View source for Action potential

{{Short description|Neuron communication by electric impulses}}
{{pp-move-vandalism|small=yes}}
{{Use dmy dates|date=March 2020}}
[[File:Action Potential.gif|thumb|upright=1.5|As an action potential (nerve impulse) travels down an [[axon]], there is a change in electric polarity across the [[cell membrane|membrane]] of the axon. In response to a signal from another [[neuron]], sodium- (Na<sup>+</sup>) and potassium- (K<sup>+</sup>){{ndash}}gated [[Voltage-gated ion channel|ion channels]] open and close as the membrane reaches its [[threshold potential]]. Na<sup>+</sup> channels open at the beginning of the action potential, and Na<sup>+</sup> moves into the axon, causing [[depolarization]]. [[Repolarization]] occurs when K<sup>+</sup> channels open and K<sup>+</sup> moves out of the axon, creating a change in electric polarity between the outside of the cell and the inside. The impulse travels down the axon in one direction only, to the [[axon terminal]] where it signals other neurons.]]

An '''action potential''' (also known as a '''nerve impulse''' or "'''spike'''" when in a [[neuron]]) is a series of quick changes in [[voltage]] across a cell membrane. An action potential occurs when the [[membrane potential]] of a specific [[Cell (biology)|cell]] rapidly rises and falls.<ref>{{cite journal | vauthors = Hodgkin AL, Huxley AF | title = A quantitative description of membrane current and its application to conduction and excitation in nerve | journal = The Journal of Physiology | volume = 117 | issue = 4 | pages = 500–44 | date = August 1952 | pmid = 12991237 | pmc = 1392413 | doi = 10.1113/jphysiol.1952.sp004764 }}</ref> This [[depolarization]] then causes adjacent locations to similarly depolarize. Action potentials occur in several types of [[Membrane potential#Cell excitability|excitable cells]], which include [[animal cell]]s like [[neuron]]s and [[myocyte|muscle cells]], as well as some [[plant cell]]s. Certain [[endocrine]] cells such as [[pancreatic beta cell]]s, and certain cells of the [[anterior pituitary gland]] are also excitable cells.<ref name="Williams">{{cite journal |vauthors=Williams JA |title=Electrical correlates of secretion in endocrine and exocrine cells |journal=Fed Proc |volume=40 |issue=2 |pages=128–34 |date=February 1981 |pmid=6257554 |doi= |url=}}</ref>

In neurons, action potentials play a central role in [[cell–cell interaction|cell–cell communication]] by providing for—or with regard to [[saltatory conduction]], assisting—the propagation of signals along the neuron's [[axon]] toward [[axon terminal|synaptic boutons]] situated at the ends of an axon; these signals can then connect with other neurons at synapses, or to motor cells or glands. In other types of cells, their main function is to activate intracellular processes. In muscle cells, for example, an action potential is the first step in the chain of events leading to contraction. In [[beta cell]]s of the [[pancreas]], they provoke release of [[insulin]].<ref group="lower-alpha" name="pmid16464129">{{cite journal | vauthors = MacDonald PE, Rorsman P | title = Oscillations, intercellular coupling, and insulin secretion in pancreatic beta cells | journal = PLOS Biology | volume = 4 | issue = 2 | pages = e49 | date = February 2006 | pmid = 16464129 | pmc = 1363709 | doi = 10.1371/journal.pbio.0040049 | doi-access = free }} {{open access}}</ref> The temporal sequence of action potentials generated by a neuron is called its "spike train". A neuron that emits an action potential, or nerve impulse, is often said to "fire".

Action potentials are generated by special types of [[voltage-gated ion channel]]s embedded in a cell's [[plasma membrane]].<ref name="pmid17515599" group=lower-alpha>{{cite journal | vauthors = Barnett MW, Larkman PM | title = The action potential | journal = Practical Neurology | volume = 7 | issue = 3 | pages = 192–7 | date = June 2007 | pmid = 17515599 | url = http://pn.bmj.com/content/7/3/192.short | url-status = live | archive-url = https://web.archive.org/web/20110708074452/http://pn.bmj.com/content/7/3/192.short | df = dmy-all | archive-date = 8 July 2011 }}</ref> These channels are shut when the membrane potential is near the (negative) [[resting potential]] of the cell, but they rapidly begin to open if the membrane potential increases to a precisely defined threshold voltage, [[depolarization|depolarising]] the transmembrane potential.<ref name="pmid17515599" group=lower-alpha /> When the channels open, they allow an inward flow of [[sodium]] ions, which changes the electrochemical gradient, which in turn produces a further rise in the membrane potential towards zero. This then causes more channels to open, producing a greater electric current across the cell membrane and so on. The process proceeds explosively until all of the available ion channels are open, resulting in a large upswing in the membrane potential. The rapid influx of sodium ions causes the polarity of the plasma membrane to reverse, and the ion channels then rapidly inactivate. As the [[sodium channel]]s close, sodium ions can no longer enter the neuron, and they are then actively transported back out of the plasma membrane. [[Potassium]] channels are then activated, and there is an outward current of potassium ions, returning the electrochemical gradient to the resting state. After an action potential has occurred, there is a transient negative shift, called the [[afterhyperpolarization]].

In animal cells, there are two primary types of action potentials. One type is generated by [[voltage-gated sodium channels]], the other by [[voltage-gated calcium channel]]s. Sodium-based action potentials usually last for under one millisecond, but calcium-based action potentials may last for 100 milliseconds or longer.{{citation needed|date=August 2020}} In some types of neurons, slow calcium spikes provide the driving force for a long burst of rapidly emitted sodium spikes. In [[cardiac action potential|cardiac muscle cells]], on the other hand, an initial fast sodium spike provides a "primer" to provoke the rapid onset of a calcium spike, which then produces muscle contraction.<ref>{{cite web |url=https://www.zoology.ubc.ca/~gardner/cardiac_muscle_contraction.htm#muscle_ap |title=Cardiac Muscle Contraction |accessdate=2021-05-28 }}</ref>

==Overview==
[[File:Action potential basic shape.svg|thumb|right|Shape of a typical action potential. The membrane potential remains near a baseline level until at some point in time, it abruptly spikes upward and then rapidly falls.]]
Nearly all [[cell membrane]]s in animals, plants and fungi maintain a [[voltage]] difference between the exterior and interior of the cell, called the [[membrane potential]]. A typical voltage across an animal cell membrane is −70 mV. This means that the interior of the cell has a negative voltage relative to the exterior. In most types of cells, the membrane potential usually stays fairly constant. Some types of cells, however, are electrically active in the sense that their voltages fluctuate over time. In some types of electrically active cells, including [[neuron]]s and muscle cells, the voltage fluctuations frequently take the form of a rapid upward (positive) spike followed by a rapid fall. These up-and-down cycles are known as ''action potentials''. In some types of neurons, the entire up-and-down cycle takes place in a few thousandths of a second. In muscle cells, a typical action potential lasts about a fifth of a second. In [[plant cell]]s, an action potential may last three seconds or more.<ref>{{Cite journal|last=Pickard|first=Barbara | name-list-style = vanc |date=June 1973|title=Action Potentials in Higher Plants|url=http://www.esalq.usp.br/lepse/imgs/conteudo_thumb/Action-Potentials-in-Higher-Plants-1.pdf|journal=The Botanical Review|volume=39|issue=2|pages=188|doi=10.1007/BF02859299|bibcode=1973BotRv..39..172P |s2cid=5026557 }}</ref>

The electrical properties of a cell are determined by the structure of its membrane. A [[cell membrane]] consists of a [[lipid bilayer]] of molecules in which larger protein molecules are embedded. The lipid bilayer is highly resistant to movement of electrically charged ions, so it functions as an insulator. The large membrane-embedded proteins, in contrast, provide channels through which ions can pass across the membrane. Action potentials are driven by channel proteins whose configuration switches between closed and open states as a function of the voltage difference between the interior and exterior of the cell. These voltage-sensitive proteins are known as [[voltage-gated ion channel]]s.{{cn|date=May 2024}}

===Process in a typical neuron===
[[File:Action potential.svg|thumb|300px|Approximate plot of a typical action potential shows its various phases as the action potential passes a point on a [[cell membrane]]. The membrane potential starts out at approximately −70 mV at time zero. A stimulus is applied at time = 1 ms, which raises the membrane potential above −55 mV (the threshold potential). After the stimulus is applied, the membrane potential rapidly rises to a peak potential of +40 mV at time = 2 ms. Just as quickly, the potential then drops and overshoots to −90 mV at time = 3 ms, and finally the resting potential of −70 mV is reestablished at time = 5 ms.]]
All cells in animal body tissues are [[Dielectric#Ionic polarization|electrically polarized]] – in other words, they maintain a voltage difference across the cell's [[plasma membrane]], known as the [[membrane potential]]. This electrical polarization results from a complex interplay between protein structures embedded in the membrane called [[Ion transporter|ion pump]]s and [[ion channel]]s. In neurons, the types of ion channels in the membrane usually vary across different parts of the cell, giving the [[dendrite]]s, [[axon]], and [[soma (biology)|cell body]] different electrical properties. As a result, some parts of the membrane of a neuron may be excitable (capable of generating action potentials), whereas others are not. Recent studies have shown that the most excitable part of a neuron is the part after the [[axon hillock]] (the point where the axon leaves the cell body), which is called the [[axonal initial segment]], but the axon and cell body are also excitable in most cases.<ref>{{cite journal | vauthors = Leterrier C | title = The Axon Initial Segment: An Updated Viewpoint | journal = The Journal of Neuroscience | volume = 38 | issue = 9 | pages = 2135–2145 | date = February 2018 | pmid = 29378864 | pmc = 6596274 | doi = 10.1523/JNEUROSCI.1922-17.2018 }}</ref>

Each excitable patch of membrane has two important levels of membrane potential: the [[resting potential]], which is the value the membrane potential maintains as long as nothing perturbs the cell, and a higher value called the [[threshold potential]]. At the axon hillock of a typical neuron, the resting potential is around –70 millivolts (mV) and the threshold potential is around –55 mV. Synaptic inputs to a neuron cause the membrane to [[depolarization|depolarize]] or [[Hyperpolarization (biology)|hyperpolarize]]; that is, they cause the membrane potential to rise or fall. Action potentials are triggered when enough depolarization accumulates to bring the membrane potential up to threshold. When an action potential is triggered, the membrane potential abruptly shoots upward and then equally abruptly shoots back downward, often ending below the resting level, where it remains for some period of time. The shape of the action potential is stereotyped; this means that the rise and fall usually have approximately the same amplitude and time course for all action potentials in a given cell. (Exceptions are discussed later in the article). In most neurons, the entire process takes place in about a thousandth of a second. Many types of neurons emit action potentials constantly at rates of up to 10–100 per second. However, some types are much quieter, and may go for minutes or longer without emitting any action potentials.

==Biophysical basis==
{{more citations needed section|date=February 2014}}

Action potentials result from the presence in a cell's membrane of special types of [[voltage-gated ion channel]]s.<ref>{{cite book |veditors=Purves D, Augustine GJ, Fitzpatrick D, et al |title=Neuroscience |edition=2nd |place=Sunderland, MA |publisher=Sinauer Associates |date=2001 |chapter=Voltage-Gated Ion Channels |chapter-url=https://www.ncbi.nlm.nih.gov/books/NBK10883/ |access-date=2017-08-29 |url-status=live |archive-url=https://web.archive.org/web/20180605025823/https://www.ncbi.nlm.nih.gov/books/NBK10883/ |archive-date=5 June 2018 |df=dmy-all }}</ref> A voltage-gated ion channel is a transmembrane protein that has three key properties:
# It is capable of assuming more than one conformation.
# At least one of the conformations creates a channel through the membrane that is permeable to specific types of ions.
# The transition between conformations is influenced by the membrane potential.

Thus, a voltage-gated ion channel tends to be open for some values of the membrane potential, and closed for others. In most cases, however, the relationship between membrane potential and channel state is probabilistic and involves a time delay. Ion channels switch between conformations at unpredictable times: The membrane potential determines the rate of transitions and the probability per unit time of each type of transition.

[[File:Blausen 0011 ActionPotential Nerve.png|thumb|300px|left|Action potential propagation along an axon]]
Voltage-gated ion channels are capable of producing action potentials because they can give rise to [[positive feedback]] loops: The membrane potential controls the state of the ion channels, but the state of the ion channels controls the membrane potential. Thus, in some situations, a rise in the membrane potential can cause ion channels to open, thereby causing a further rise in the membrane potential. An action potential occurs when this positive feedback cycle ([[Hodgkin cycle]]) proceeds explosively. The time and amplitude trajectory of the action potential are determined by the biophysical properties of the voltage-gated ion channels that produce it. Several types of channels capable of producing the positive feedback necessary to generate an action potential do exist. Voltage-gated sodium channels are responsible for the fast action potentials involved in nerve conduction. Slower action potentials in muscle cells and some types of neurons are generated by voltage-gated calcium channels. Each of these types comes in multiple variants, with different voltage sensitivity and different temporal dynamics.

The most intensively studied type of voltage-dependent ion channels comprises the sodium channels involved in fast nerve conduction. These are sometimes known as Hodgkin-Huxley sodium channels because they were first characterized by [[Alan Lloyd Hodgkin|Alan Hodgkin]] and [[Andrew Huxley]] in their Nobel Prize-winning studies of the biophysics of the action potential, but can more conveniently be referred to as ''Na''<sub>V</sub> channels. (The "V" stands for "voltage".) An ''Na''<sub>V</sub> channel has three possible states, known as ''deactivated'', ''activated'', and ''inactivated''. The channel is permeable only to sodium ions when it is in the ''activated'' state. When the membrane potential is low, the channel spends most of its time in the ''deactivated'' (closed) state. If the membrane potential is raised above a certain level, the channel shows increased probability of transitioning to the ''activated'' (open) state. The higher the membrane potential the greater the probability of activation. Once a channel has activated, it will eventually transition to the ''inactivated'' (closed) state. It tends then to stay inactivated for some time, but, if the membrane potential becomes low again, the channel will eventually transition back to the ''deactivated'' state. During an action potential, most channels of this type go through a cycle ''deactivated''→''activated''→''inactivated''→''deactivated''. This is only the population average behavior, however – an individual channel can in principle make any transition at any time. However, the likelihood of a channel's transitioning from the ''inactivated'' state directly to the ''activated'' state is very low: A channel in the ''inactivated'' state is refractory until it has transitioned back to the ''deactivated'' state.

The outcome of all this is that the kinetics of the ''Na''<sub>V</sub> channels are governed by a transition matrix whose rates are voltage-dependent in a complicated way. Since these channels themselves play a major role in determining the voltage, the global dynamics of the system can be quite difficult to work out. Hodgkin and Huxley approached the problem by developing a set of [[differential equation]]s for the parameters that govern the ion channel states, known as the [[Hodgkin–Huxley model|Hodgkin-Huxley equations]]. These equations have been extensively modified by later research, but form the starting point for most theoretical studies of action potential biophysics.

[[File:Membrane Permeability of a Neuron During an Action Potential.svg|thumb|upright=1.75|right|Ion movement during an action potential.<br />''Key:'' a) Sodium (Na<sup>+</sup>) ion. b) Potassium (K<sup>+</sup>) ion. c) Sodium channel. d) Potassium channel. e) Sodium-potassium pump.<br /> In the stages of an action potential, the permeability of the membrane of the neuron changes. At the '''resting state''' (1), sodium and potassium ions have limited ability to pass through the membrane, and the neuron has a net negative charge inside. Once the action potential is triggered, the '''depolarization''' (2) of the neuron activates sodium channels, allowing sodium ions to pass through the cell membrane into the cell, resulting in a net positive charge in the neuron relative to the extracellular fluid. After the action potential peak is reached, the neuron begins '''repolarization''' (3), where the sodium channels close and potassium channels open, allowing potassium ions to cross the membrane into the extracellular fluid, returning the membrane potential to a negative value. Finally, there is a '''refractory period''' (4), during which the voltage-dependent ion channels are [[Voltage-gated ion channel#Mechanism|inactivated]] while the Na<sup>+</sup> and K<sup>+</sup> ions return to their resting state distributions across the membrane (1), and the neuron is ready to repeat the process for the next action potential.]]

{{Anchor|Firing rate|Neural firing rate}}<!-- This anchor is for the bolded terms at the end of this paragraph; if that sentence is moved, this anchor should be moved along with that sentence to the same location in this article.
-->As the membrane potential is increased, [[sodium channel|sodium ion channels]] open, allowing the entry of [[sodium]] ions into the cell. This is followed by the opening of [[potassium channel|potassium ion channels]] that permit the exit of [[potassium]] ions from the cell. The inward flow of sodium ions increases the concentration of positively charged [[cation]]s in the cell and causes depolarization, where the potential of the cell is higher than the cell's [[resting potential]]. The sodium channels close at the peak of the action potential, while potassium continues to leave the cell. The efflux of potassium ions decreases the membrane potential or hyperpolarizes the cell. For small voltage increases from rest, the potassium current exceeds the sodium current and the voltage returns to its normal resting value, typically −70&nbsp;mV.{{sfn|Bullock|Orkand|Grinnell|1977|pp=150–151}}{{sfn|Junge|1981|pp=89–90}}{{sfn|Schmidt-Nielsen|1997|p=484}} However, if the voltage increases past a critical threshold, typically 15&nbsp;mV higher than the resting value, the sodium current dominates. This results in a runaway condition whereby the [[positive feedback]] from the sodium current activates even more sodium channels. Thus, the cell ''fires'', producing an action potential.{{sfn|Bullock|Orkand|Grinnell|1977|pp=150–151}}{{sfnm|1a1=Purves|1a2=Augustine|1a3=Fitzpatrick|1a4=Hall|1y=2008|1pp=48–49|2a1=Bullock|2a2=Orkand|2a3=Grinnell|2y=1977|2p=141|3a1=Schmidt-Nielsen|3y=1997|3p=483|4a1=Junge|4y=1981|4p=89}}{{sfn|Stevens|1966|p=127}}{{refn|In general, while this simple description of action potential initiation is accurate, it does not explain phenomena such as excitation block (the ability to prevent neurons from eliciting action potentials by stimulating them with large current steps) and the ability to elicit action potentials by briefly hyperpolarizing the membrane. By analyzing the dynamics of a system of sodium and potassium channels in a membrane patch using [[computational model]]s, however, these phenomena are readily explained.<ref group=lower-Greek>{{cite journal|title=FitzHugh-Nagumo model|journal=Scholarpedia|volume=1|issue=9|pages=1349|df=dmy-all|doi=10.4249/scholarpedia.1349|year=2006|last1=Fitzhugh|first1=Richard|last2=Izhikevich|first2=Eugene | name-list-style = vanc |bibcode=2006SchpJ...1.1349I|doi-access=free}}</ref>|group="note"}} The frequency at which a neuron elicits action potentials is often referred to as a '''firing rate''' or '''neural firing rate'''.<!--"Neural firing rate" redirects here; these terms are bolded per MOS:BOLD.-->

Currents produced by the opening of voltage-gated channels in the course of an action potential are typically significantly larger than the initial stimulating current. Thus, the amplitude, duration, and shape of the action potential are determined largely by the properties of the excitable membrane and not the amplitude or duration of the stimulus. This [[All-or-none law|all-or-nothing]] property of the action potential sets it apart from [[graded potential]]s such as [[receptor potential]]s, [[electrotonic potential]]s, [[subthreshold membrane potential oscillations]], and [[synaptic potential]]s, which scale with the magnitude of the stimulus. A variety of action potential types exist in many cell types and cell compartments as determined by the types of voltage-gated channels, [[leak channels]], channel distributions, ionic concentrations, membrane capacitance, temperature, and other factors.

The principal ions involved in an action potential are sodium and potassium cations; sodium ions enter the cell, and potassium ions leave, restoring equilibrium. Relatively few ions need to cross the membrane for the membrane voltage to change drastically. The ions exchanged during an action potential, therefore, make a negligible change in the interior and exterior ionic concentrations. The few ions that do cross are pumped out again by the continuous action of the [[sodium–potassium pump]], which, with other [[ion transporter]]s, maintains the normal ratio of ion concentrations across the membrane. [[Calcium]] cations and [[chloride]] [[anion]]s are involved in a few types of action potentials, such as the [[cardiac action potential]] and the action potential in the single-cell [[algae|alga]] ''[[Acetabularia]]'', respectively.

Although action potentials are generated locally on patches of excitable membrane, the resulting currents can trigger action potentials on neighboring stretches of membrane, precipitating a domino-like propagation. In contrast to passive spread of electric potentials ([[electrotonic potential]]), action potentials are generated anew along excitable stretches of membrane and propagate without decay.<ref name="no_decrement">[[Knut Schmidt-Nielsen|Schmidt-Nielsen]], p. 484.</ref> Myelinated sections of axons are not excitable and do not produce action potentials and the signal is propagated passively as [[electrotonic potential]]. Regularly spaced unmyelinated patches, called the [[nodes of Ranvier]], generate action potentials to boost the signal. Known as [[saltatory conduction]], this type of signal propagation provides a favorable tradeoff of signal velocity and axon diameter. Depolarization of [[axon terminal]]s, in general, triggers the release of [[neurotransmitter]] into the [[synaptic cleft]]. In addition, backpropagating action potentials have been recorded in the dendrites of [[pyramidal cell|pyramidal neurons]], which are ubiquitous in the neocortex.<ref name="backpropagation_in_pyramidal_cells" group=lower-alpha>{{cite journal | vauthors = Golding NL, Kath WL, Spruston N | title = Dichotomy of action-potential backpropagation in CA1 pyramidal neuron dendrites | journal = Journal of Neurophysiology | volume = 86 | issue = 6 | pages = 2998–3010 | date = December 2001 | pmid = 11731556 | doi = 10.1152/jn.2001.86.6.2998 | s2cid = 2915815 | df = dmy-all }}</ref> These are thought to have a role in [[spike-timing-dependent plasticity]].

In the [[Hodgkin–Huxley model|Hodgkin–Huxley membrane capacitance model]], the speed of transmission of an action potential was undefined and it was assumed that adjacent areas became depolarized due to released ion interference with neighbouring channels. Measurements of ion diffusion and radii have since shown this not to be possible.{{citation needed|date=November 2019}} Moreover, contradictory measurements of entropy changes and timing disputed the capacitance model as acting alone.{{citation needed|date=November 2019}} Alternatively, Gilbert Ling's adsorption hypothesis, posits that the membrane potential and action potential of a living cell is due to the adsorption of mobile ions onto adsorption sites of cells.<ref>{{cite journal | vauthors = Tamagawa H, Funatani M, Ikeda K | title = Ling's Adsorption Theory as a Mechanism of Membrane Potential Generation Observed in Both Living and Nonliving Systems | journal = Membranes | volume = 6 | issue = 1 | pages = 11 | date = January 2016 | pmid = 26821050 | pmc = 4812417 | doi = 10.3390/membranes6010011 | doi-access = free }}</ref>

=== Maturation of the electrical properties of the action potential ===
A [[neuron]]'s ability to generate and propagate an action potential changes during [[Neural development|development]]. How much the [[membrane potential]] of a neuron changes as the result of a current impulse is a function of the membrane [[Input impedance|input resistance]]. As a cell grows, more [[Ion channel|channels]] are added to the membrane, causing a decrease in input resistance. A mature neuron also undergoes shorter changes in membrane potential in response to synaptic currents. Neurons from a ferret [[lateral geniculate nucleus]] have a longer [[time constant]] and larger [[voltage]] deflection at P0 than they do at P30.<ref name=":0">{{Cite book|title=Development of the nervous system|last1=Sanes|first1=Dan H.|last2=Reh|first2=Thomas A | name-list-style = vanc |date=2012-01-01|publisher=Elsevier Academic Press|isbn=9780080923208|pages=211–214|oclc=762720374|edition=Third}}</ref> One consequence of the decreasing action potential duration is that the fidelity of the signal can be preserved in response to high frequency stimulation. Immature neurons are more prone to synaptic depression than potentiation after high frequency stimulation.<ref name=":0" />

In the early development of many organisms, the action potential is actually initially carried by [[Calcium channel|calcium current]] rather than [[Sodium channel|sodium current]]. The [[Gating (electrophysiology)|opening and closing kinetics]] of calcium channels during development are slower than those of the voltage-gated sodium channels that will carry the action potential in the mature neurons. The longer opening times for the calcium channels can lead to action potentials that are considerably slower than those of mature neurons.<ref name=":0" /> [[Xenopus]] neurons initially have action potentials that take 60–90 ms. During development, this time decreases to 1 ms. There are two reasons for this drastic decrease. First, the [[Depolarization|inward current]] becomes primarily carried by sodium channels.<ref>{{Cite book|title=Calcium Channels: Their Properties, Functions, Regulation, and Clinical relevance|last=Partridge|first=Donald | name-list-style = vanc |publisher=CRC Press|year=1991|isbn=9780849388071|pages=138–142}}</ref> Second, the [[Voltage-gated potassium channel|delayed rectifier]], a [[potassium channel]] current, increases to 3.5 times its initial strength.<ref name=":0" />

In order for the transition from a calcium-dependent action potential to a sodium-dependent action potential to proceed new channels must be added to the membrane. If Xenopus neurons are grown in an environment with [[Transcription (biology)|RNA synthesis]] or [[Translation (biology)|protein synthesis]] inhibitors that transition is prevented.<ref>{{Cite book|url=https://www.springer.com/us/book/9780306415500|title=Cellular and Molecular Biology of Neuronal Development {{!}} Ira Black {{!}} Springer|last=Black|first=Ira | name-list-style = vanc |publisher=Springer|year=1984|isbn=978-1-4613-2717-2|pages=103|language=en|url-status=live|archive-url=https://web.archive.org/web/20170717154858/http://www.springer.com/us/book/9780306415500|archive-date=17 July 2017|df=dmy-all}}</ref> Even the electrical activity of the cell itself may play a role in channel expression. If action potentials in Xenopus [[myocyte]]s are blocked, the typical increase in sodium and potassium current density is prevented or delayed.<ref>{{Cite book|title=Current Topics in Developmental Biology, Volume 39|last=Pedersen|first=Roger | name-list-style = vanc |publisher=Elsevier Academic Press|year=1998|isbn=9780080584621|url=https://archive.org/details/currenttopicsind0000unse_x6e1}}</ref>

This maturation of electrical properties is seen across species. Xenopus sodium and potassium currents increase drastically after a neuron goes through its final phase of [[mitosis]]. The sodium current density of rat [[Cerebral cortex|cortical neurons]] increases by 600% within the first two postnatal weeks.<ref name=":0" />

==Neurotransmission==
{{Main|Neurotransmission}}

===Anatomy of a neuron===
{{Neuron map}}
Several types of cells support an action potential, such as plant cells, muscle cells, and the specialized cells of the heart (in which occurs the [[cardiac action potential]]). However, the main excitable cell is the [[neuron]], which also has the simplest mechanism for the action potential.{{cn|date=May 2024}}

Neurons are electrically excitable cells composed, in general, of one or more dendrites, a single [[soma (biology)|soma]], a single axon and one or more [[axon terminal]]s. Dendrites are cellular projections whose primary function is to receive synaptic signals. Their protrusions, known as [[dendritic spine]]s, are designed to capture the neurotransmitters released by the presynaptic neuron. They have a high concentration of [[ligand-gated ion channel]]s. These spines have a thin neck connecting a bulbous protrusion to the dendrite. This ensures that changes occurring inside the spine are less likely to affect the neighboring spines. The dendritic spine can, with rare exception (see [[Long-term potentiation#Properties|LTP]]), act as an independent unit. The dendrites extend from the soma, which houses the [[Cell nucleus|nucleus]], and many of the "normal" [[eukaryote|eukaryotic]] organelles. Unlike the spines, the surface of the soma is populated by voltage activated ion channels. These channels help transmit the signals generated by the dendrites. Emerging out from the soma is the [[axon hillock]]. This region is characterized by having a very high concentration of voltage-activated sodium channels. In general, it is considered to be the spike initiation zone for action potentials,{{sfn|Bullock|Orkand|Grinnell|1977|p=11}} i.e. the [[trigger zone]]. Multiple signals generated at the spines, and transmitted by the soma all converge here. Immediately after the axon hillock is the axon. This is a thin tubular protrusion traveling away from the soma. The axon is insulated by a [[myelin]] sheath. Myelin is composed of either [[Schwann cells]] (in the peripheral nervous system) or [[oligodendrocytes]] (in the central nervous system), both of which are types of [[glial cells]]. Although glial cells are not involved with the transmission of electrical signals, they communicate and provide important biochemical support to neurons.{{sfn|Silverthorn|2010|p=253}} To be specific, myelin wraps multiple times around the axonal segment, forming a thick fatty layer that prevents ions from entering or escaping the axon. This insulation prevents significant signal decay as well as ensuring faster signal speed. This insulation, however, has the restriction that no channels can be present on the surface of the axon. There are, therefore, regularly spaced patches of membrane, which have no insulation. These [[nodes of Ranvier]] can be considered to be "mini axon hillocks", as their purpose is to boost the signal in order to prevent significant signal decay. At the furthest end, the axon loses its insulation and begins to branch into several [[axon terminal]]s. These presynaptic terminals, or synaptic boutons, are a specialized area within the axon of the presynaptic cell that contains [[neurotransmitters]] enclosed in small membrane-bound spheres called [[synaptic vesicle]]s.{{cn|date=May 2024}}

===Initiation===
Before considering the propagation of action potentials along [[axon]]s and their termination at the synaptic knobs, it is helpful to consider the methods by which action potentials can be initiated at the [[axon hillock]]. The basic requirement is that the membrane voltage at the hillock be raised above the threshold for firing.{{sfn|Bullock|Orkand|Grinnell|1977|pp=150–151}}{{sfn|Junge|1981|pp=89–90}}{{sfnm|1a1=Purves|1a2=Augustine|1a3=Fitzpatrick|1a4=Hall|1y=2008|1pp=49–50|2a1=Bullock|2a2=Orkand|2a3=Grinnell|2y=1977|2pp=140–141|3a1=Schmidt-Nielsen|3y=1997|3pp=480-481}}{{sfn|Schmidt-Nielsen|1997|pp=483-484}} There are several ways in which this depolarization can occur.
{{clear}}
[[Image:SynapseSchematic en.svg|thumb|right|300px|When an action potential arrives at the end of the pre-synaptic axon (top), it causes the release of [[neurotransmitter]] molecules that open ion channels in the post-synaptic neuron (bottom). The combined [[excitatory postsynaptic potential|excitatory]] and [[inhibitory postsynaptic potential]]s of such inputs can begin a new action potential in the post-synaptic neuron.|alt=The pre- and post-synaptic axons are separated by a short distance known as the synaptic cleft. Neurotransmitter released by pre-synaptic axons diffuse through the synaptic clef to bind to and open ion channels in post-synaptic axons.]]

===Dynamics===
Action potentials are most commonly initiated by [[excitatory postsynaptic potential]]s from a presynaptic neuron.{{sfnm|1a1=Bullock|1a2=Orkand|1a3=Grinnell|1y=1977|1pp=177–240|2a1=Schmidt-Nielsen|2y=1997|2pp=490-499|3a1=Stevens|3y=1966|3p=47–68}} Typically, [[neurotransmitter]] molecules are released by the [[synapse|presynaptic]] [[neuron]]. These neurotransmitters then bind to receptors on the postsynaptic cell. This binding opens various types of [[ion channel]]s. This opening has the further effect of changing the local permeability of the [[cell membrane]] and, thus, the membrane potential. If the binding increases the voltage (depolarizes the membrane), the synapse is excitatory. If, however, the binding decreases the voltage (hyperpolarizes the membrane), it is inhibitory. Whether the voltage is increased or decreased, the change propagates passively to nearby regions of the membrane (as described by the [[cable equation]] and its refinements). Typically, the voltage stimulus decays exponentially with the distance from the synapse and with time from the binding of the neurotransmitter. Some fraction of an excitatory voltage may reach the [[axon hillock]] and may (in rare cases) depolarize the membrane enough to provoke a new action potential. More typically, the excitatory potentials from several synapses must [[spatial summation|work together]] at [[temporal summation|nearly the same time]] to provoke a new action potential. Their joint efforts can be thwarted, however, by the counteracting [[inhibitory postsynaptic potential]]s.{{cn|date=May 2024}}

Neurotransmission can also occur through [[electrical synapse]]s.{{sfnm|1a1=Bullock|1a2=Orkand|1a3=Grinnell|1y=1977|1pp=178–180|2a1=Schmidt-Nielsen|2y=1997|2pp=490-491}} Due to the direct connection between excitable cells in the form of [[gap junction]]s, an action potential can be transmitted directly from one cell to the next in either direction. The free flow of ions between cells enables rapid non-chemical-mediated transmission. Rectifying channels ensure that action potentials move only in one direction through an electrical synapse.{{Citation needed|date=May 2011}} Electrical synapses are found in all nervous systems, including the human brain, although they are a distinct minority.{{sfn|Purves|Augustine|Fitzpatrick|Hall|2001}}

==="All-or-none" principle===
{{Main|All-or-none law}}
The [[amplitude]] of an action potential is often thought to be independent of the amount of current that produced it. In other words, larger currents do not create larger action potentials. Therefore, action potentials are said to be [[All-or-none law|all-or-none]] signals, since either they occur fully or they do not occur at all.<ref name=" Sasaki " group=lower-alpha>Sasaki, T., Matsuki, N., Ikegaya, Y. 2011 Action-potential modulation during axonal conduction Science 331 (6017), pp. 599–601</ref><ref name="Aur" group=lower-alpha>{{cite journal | vauthors = Aur D, Connolly CI, Jog MS | title = Computing spike directivity with tetrodes | journal = Journal of Neuroscience Methods | volume = 149 | issue = 1 | pages = 57–63 | date = November 2005 | pmid = 15978667 | doi = 10.1016/j.jneumeth.2005.05.006 | s2cid = 34131910 }}</ref><ref name="Aur, Jog" group=lower-alpha>Aur D., Jog, MS., 2010 Neuroelectrodynamics: Understanding the brain language, IOS Press, 2010. {{doi|10.3233/978-1-60750-473-3-i}}</ref> This is in contrast to [[receptor potential]]s, whose amplitudes are dependent on the intensity of a stimulus.{{sfn|Purves|Augustine|Fitzpatrick|Hall|2008|pp=26–28}} In both cases, the [[frequency]] of action potentials is correlated with the intensity of a stimulus.

Despite the classical view of the action potential as a stereotyped, uniform signal having dominated the field of neuroscience for many decades, newer evidence does suggest that action potentials are more complex events indeed capable of transmitting information through not just their amplitude, but their duration and phase as well, sometimes even up to distances originally not thought to be possible.<ref>{{cite journal |title=Myelination Increases the Spatial Extent of Analog Modulation of Synaptic Transmission: A Modeling Study |url=https://www.researchgate.net/publication/339655307|journal=Frontiers in Cellular Neuroscience}}</ref><ref>{{cite journal |title=Past and Future of Analog-Digital Modulation of Synaptic Transmission |year=2019 |pmc=6492051 |last1=Zbili |first1=M. |last2=Debanne |first2=D. |journal=Frontiers in Cellular Neuroscience |volume=13 |page=160 |doi=10.3389/fncel.2019.00160 |pmid=31105529 |doi-access=free }}</ref><ref>{{cite journal |title=Neural Coding: Analog Signalling in Axons | journal=Current Biology | date=8 August 2006 | volume=16 | issue=15 | pages=R585–R588 | doi=10.1016/j.cub.2006.07.007 | last1=Clark | first1=Beverley | last2=Häusser | first2=Michael | pmid=16890514 | s2cid=8295969 | doi-access=free }}</ref><ref>{{cite journal |title=Analog transmission of action potential fine structure in spiral ganglion axons |year=2021 |doi=10.1152/jn.00237.2021 |last1=Liu |first1=Wenke |last2=Liu |first2=Qing |last3=Crozier |first3=Robert A. |last4=Davis |first4=Robin L. |journal=Journal of Neurophysiology |volume=126 |issue=3 |pages=888–905 |pmid=34346782 |pmc=8461829 }}</ref>

===Sensory neurons===
{{Main|Sensory neuron}}

In [[sensory neurons]], an external signal such as pressure, temperature, light, or sound is coupled with the opening and closing of [[ion channels]], which in turn alter the ionic permeabilities of the membrane and its voltage.{{sfnm|1a1=Schmidt-Nielsen|1y=1997|1pp=535–580|2a1=Bullock|2a2=Orkand|2a3=Grinnell|2y=1977|2pp=49–56, 76–93, 247–255|3a1=Stevens|3y=1966|3pp=69–79}} These voltage changes can again be excitatory (depolarizing) or inhibitory (hyperpolarizing) and, in some sensory neurons, their combined effects can depolarize the axon hillock enough to provoke action potentials. Some examples in humans include the [[olfactory receptor neuron]] and [[Meissner's corpuscle]], which are critical for the sense of [[olfaction|smell]] and [[somatosensory system|touch]], respectively. However, not all sensory neurons convert their external signals into action potentials; some do not even have an axon.{{sfnm|1a1=Bullock|1a2=Orkand|1a3=Grinnell|1y=1977|1pp=53|2a1=Bullock|2a2=Orkand|2a3=Grinnell|2y=1977|2pp=122–124}} Instead, they may convert the signal into the release of a [[neurotransmitter]], or into continuous [[receptor potential|graded potentials]], either of which may stimulate subsequent neuron(s) into firing an action potential. For illustration, in the human [[ear]], [[hair cell]]s convert the incoming sound into the opening and closing of [[stretch-activated ion channel|mechanically gated ion channels]], which may cause [[neurotransmitter]] molecules to be released. In similar manner, in the human [[retina]], the initial [[photoreceptor cell]]s and the next layer of cells (comprising [[bipolar cell]]s and [[horizontal cell]]s) do not produce action potentials; only some [[amacrine cell]]s and the third layer, the [[Retinal ganglion cell|ganglion cell]]s, produce action potentials, which then travel up the [[optic nerve]].{{cn|date=May 2024}}

===Pacemaker potentials===
{{Main|Pacemaker potential}}

[[Image:Pacemaker potential.svg|thumb|right|In [[pacemaker potential]]s, the cell spontaneously depolarizes (straight line with upward slope) until it fires an action potential.|alt=A plot of action potential (mV) vs time. The membrane potential is initially −60 mV, rise relatively slowly to the threshold potential of −40 mV, and then quickly spikes at a potential of +10 mV, after which it rapidly returns to the starting −60 mV potential. The cycle is then repeated.]]

In sensory neurons, action potentials result from an external stimulus. However, some excitable cells require no such stimulus to fire: They spontaneously depolarize their axon hillock and fire action potentials at a regular rate, like an internal clock.{{sfn|Junge|1981|pp=115–132}} The voltage traces of such cells are known as [[pacemaker potential]]s.{{sfn|Bullock|Orkand|Grinnell|1977|pp=152–153}} The [[cardiac pacemaker]] cells of the [[sinoatrial node]] in the [[heart]] provide a good example.<ref name="noble_1960" group=lower-alpha >{{cite journal | vauthors = Noble D | title = Cardiac action and pacemaker potentials based on the Hodgkin-Huxley equations | journal = Nature | volume = 188 | issue = 4749 | pages = 495–7 | date = November 1960 | pmid = 13729365 | doi = 10.1038/188495b0 | bibcode = 1960Natur.188..495N | s2cid = 4147174 }}</ref> Although such pacemaker potentials have a [[neural oscillation|natural rhythm]], it can be adjusted by external stimuli; for instance, [[heart rate]] can be altered by pharmaceuticals as well as signals from the [[sympathetic nervous system|sympathetic]] and [[parasympathetic nervous system|parasympathetic]] nerves.{{sfn|Bullock|Orkand|Grinnell|1977|pp=444–445}} The external stimuli do not cause the cell's repetitive firing, but merely alter its timing.{{sfn|Bullock|Orkand|Grinnell|1977|pp=152–153}} In some cases, the regulation of frequency can be more complex, leading to patterns of action potentials, such as [[bursting]].{{cn|date=May 2024}}

==Phases==
The course of the action potential can be divided into five parts: the rising phase, the peak phase, the falling phase, the undershoot phase, and the refractory period. During the rising phase the membrane potential depolarizes (becomes more positive). The point at which [[depolarization]] stops is called the peak phase. At this stage, the membrane potential reaches a maximum. Subsequent to this, there is a falling phase. During this stage the membrane potential becomes more negative, returning towards resting potential. The undershoot, or [[afterhyperpolarization]], phase is the period during which the membrane potential temporarily becomes more negatively charged than when at rest (hyperpolarized). Finally, the time during which a subsequent action potential is impossible or difficult to fire is called the [[refractory period (physiology)|refractory period]], which may overlap with the other phases.{{sfn|Purves|Augustine|Fitzpatrick|Hall|2008|p=38}}

The course of the action potential is determined by two coupled effects.{{sfn|Stevens|1966|pp=127–128}} First, voltage-sensitive ion channels open and close in response to changes in the [[membrane potential|membrane voltage]] ''V<sub>m</sub>''. This changes the membrane's permeability to those ions.{{sfn|Purves|Augustine|Fitzpatrick|Hall|2008|pp=61–65}} Second, according to the [[Goldman equation]], this change in permeability changes the equilibrium potential ''E<sub>m</sub>'', and, thus, the membrane voltage ''V<sub>m</sub>''.<ref name="goldman_1943" group=lower-alpha /> Thus, the membrane potential affects the permeability, which then further affects the membrane potential. This sets up the possibility for [[positive feedback]], which is a key part of the rising phase of the action potential.{{sfn|Bullock|Orkand|Grinnell|1977|pp=150–151}}{{sfnm|1a1=Purves|1a2=Augustine|1a3=Fitzpatrick|1a4=Hall|1y=2008|1pp=48–49|2a1=Bullock|2a2=Orkand|2a3=Grinnell|2y=1977|2p=141|3a1=Schmidt-Nielsen|3y=1997|3p=483|4a1=Junge|4y=1981|4p=89}} A complicating factor is that a single ion channel may have multiple internal "gates" that respond to changes in ''V<sub>m</sub>'' in opposite ways, or at different rates.{{sfnm|1a1=Purves|1a2=Augustine|1a3=Fitzpatrick|1a4=Hall|1y=2008|1pp=64–74|2a1=Bullock|2a2=Orkand|2a3=Grinnell|2y=1977|2pp=149–150|3a1=Junge|3y=1981|3pp=84–85|4a1=Stevens|4y=1966|4pp=152–158}}<ref name="hodgkin_1952" group=lower-alpha /> For example, although raising ''V<sub>m</sub>'' ''opens'' most gates in the voltage-sensitive sodium channel, it also ''closes'' the channel's "inactivation gate", albeit more slowly.{{sfnm|1a1=Purves|1a2=Augustine|1a3=Fitzpatrick|1a4=Hall|1y=2008|1p=47|2a1=Purves|2a2=Augustine|2a3=Fitzpatrick|2a4=Hall|2y=2008|2p=65|3a1=Bullock|3a2=Orkand|3a3=Grinnell|3y=1977|3pp=147–148|4a1=Stevens|4y=1966|4p=128}} Hence, when ''V<sub>m</sub>'' is raised suddenly, the sodium channels open initially, but then close due to the slower inactivation.

The voltages and currents of the action potential in all of its phases were modeled accurately by [[Alan Lloyd Hodgkin]] and [[Andrew Huxley]] in 1952,<ref name="hodgkin_1952" group=lower-alpha /> for which they were awarded the [[Nobel Prize in Physiology or Medicine]] in 1963.<ref name="Nobel_1963" group=lower-Greek>{{cite press release | url = http://nobelprize.org/nobel_prizes/medicine/laureates/1963/index.html | title = The Nobel Prize in Physiology or Medicine 1963 | publisher = The Royal Swedish Academy of Science | year = 1963 | access-date = 2010-02-21 | url-status = live | archive-url = https://web.archive.org/web/20070716195411/http://nobelprize.org/nobel_prizes/medicine/laureates/1963/index.html | archive-date = 16 July 2007 | df = dmy-all }}</ref> However, [[Hodgkin–Huxley model|their model]] considers only two types of voltage-sensitive ion channels, and makes several assumptions about them, e.g., that their internal gates open and close independently of one another. In reality, there are many types of ion channels,<ref name="goldin_2007">Goldin, AL in {{harvnb|Waxman|2007|loc=''Neuronal Channels and Receptors'', pp. 43–58.}}</ref> and they do not always open and close independently.<ref group=lower-alpha>{{cite journal | vauthors = Naundorf B, Wolf F, Volgushev M | title = Unique features of action potential initiation in cortical neurons | journal = Nature | volume = 440 | issue = 7087 | pages = 1060–3 | date = April 2006 | pmid = 16625198 | doi = 10.1038/nature04610 | url = http://www.volgushev.uconn.edu/DownLoads/Naundorf_Nature2006v440p1060_Suppl_3_CoopModel.pdf | df = dmy-all | bibcode = 2006Natur.440.1060N | s2cid = 1328840 | access-date = 24 September 2019 | archive-date = 20 December 2018 | archive-url = https://web.archive.org/web/20181220232812/http://volgushev.uconn.edu/DownLoads/Naundorf_Nature2006v440p1060_Suppl_3_CoopModel.pdf | url-status = dead }}</ref>

===Stimulation and rising phase===
A typical action potential begins at the [[axon hillock]]{{sfn|Stevens|1966|p=49}} with a sufficiently strong depolarization, e.g., a stimulus that increases ''V<sub>m</sub>''. This depolarization is often caused by the injection of extra sodium [[cation]]s into the cell; these cations can come from a wide variety of sources, such as [[chemical synapse]]s, [[sensory neuron]]s or [[pacemaker potential]]s.{{cn|date=May 2024}}

For a neuron at rest, there is a high concentration of sodium and chloride ions in the [[extracellular fluid]] compared to the [[intracellular fluid]], while there is a high concentration of potassium ions in the intracellular fluid compared to the extracellular fluid. The difference in concentrations, which causes ions to move [[Second law of thermodynamics|from a high to a low concentration]], and electrostatic effects (attraction of opposite charges) are responsible for the movement of ions in and out of the neuron. The inside of a neuron has a negative charge, relative to the cell exterior, from the movement of K<sup>+</sup> out of the cell. The neuron membrane is more permeable to K<sup>+</sup> than to other ions, allowing this ion to selectively move out of the cell, down its concentration gradient. This concentration gradient along with [[potassium leak channel]]s present on the membrane of the neuron causes an [[wikt:Special:Search/efflux|efflux]] of potassium ions making the resting potential close to ''E''<sub>K</sub>&nbsp;≈&nbsp;–75&nbsp;mV.{{sfnm|1a1=Purves|1a2=Augustine|1a3=Fitzpatrick|1a4=Hall|1y=2008|1p=34|2a1=Bullock|2a2=Orkand|2a3=Grinnell|2y=1977|2p=134|3a1=Schmidt-Nielsen|3y=1997|3pp=478–480}} Since Na<sup>+</sup> ions are in higher concentrations outside of the cell, the concentration and voltage differences both drive them into the cell when Na<sup>+</sup> channels open. Depolarization opens both the sodium and potassium channels in the membrane, allowing the ions to flow into and out of the axon, respectively. If the depolarization is small (say, increasing ''V<sub>m</sub>'' from −70&nbsp;mV to −60&nbsp;mV), the outward potassium current overwhelms the inward sodium current and the membrane repolarizes back to its normal resting potential around −70&nbsp;mV.{{sfn|Bullock|Orkand|Grinnell|1977|pp=150–151}}{{sfn|Junge|1981|pp=89–90}}{{sfn|Schmidt-Nielsen|1997|p=484}} However, if the depolarization is large enough, the inward sodium current increases more than the outward potassium current and a runaway condition ([[positive feedback]]) results: the more inward current there is, the more ''V<sub>m</sub>'' increases, which in turn further increases the inward current.{{sfn|Bullock|Orkand|Grinnell|1977|pp=150–151}}{{sfnm|1a1=Purves|1a2=Augustine|1a3=Fitzpatrick|1a4=Hall|1y=2008|1pp=48–49|2a1=Bullock|2a2=Orkand|2a3=Grinnell|2y=1977|2p=141|3a1=Schmidt-Nielsen|3y=1997|3p=483|4a1=Junge|4y=1981|4p=89}} A sufficiently strong depolarization (increase in ''V<sub>m</sub>'') causes the voltage-sensitive sodium channels to open; the increasing permeability to sodium drives ''V<sub>m</sub>'' closer to the sodium equilibrium voltage ''E''<sub>Na</sub>≈ +55&nbsp;mV. The increasing voltage in turn causes even more sodium channels to open, which pushes ''V<sub>m</sub>'' still further towards ''E''<sub>Na</sub>. This positive feedback continues until the sodium channels are fully open and ''V<sub>m</sub>'' is close to ''E''<sub>Na</sub>.{{sfn|Bullock|Orkand|Grinnell|1977|pp=150–151}}{{sfn|Junge|1981|pp=89–90}}{{sfnm|1a1=Purves|1a2=Augustine|1a3=Fitzpatrick|1a4=Hall|1y=2008|1pp=49–50|2a1=Bullock|2a2=Orkand|2a3=Grinnell|2y=1977|2pp=140–141|3a1=Schmidt-Nielsen|3y=1997|3pp=480–481}}{{sfn|Schmidt-Nielsen|1997|pp=483–484}} The sharp rise in ''V<sub>m</sub>'' and sodium permeability correspond to the ''rising phase'' of the action potential.{{sfn|Bullock|Orkand|Grinnell|1977|pp=150–151}}{{sfn|Junge|1981|pp=89–90}}{{sfnm|1a1=Purves|1a2=Augustine|1a3=Fitzpatrick|1a4=Hall|1y=2008|1pp=49–50|2a1=Bullock|2a2=Orkand|2a3=Grinnell|2y=1977|2pp=140–141|3a1=Schmidt-Nielsen|3y=1997|3pp=480–481}}{{sfn|Schmidt-Nielsen|1997|pp=483–484}}

The critical threshold voltage for this runaway condition is usually around −45&nbsp;mV, but it depends on the recent activity of the axon. A cell that has just fired an action potential cannot fire another one immediately, since the Na<sup>+</sup> channels have not recovered from the inactivated state. The period during which no new action potential can be fired is called the ''absolute refractory period''.{{sfn|Purves|Augustine|Fitzpatrick|Hall|2008|p=49}}{{sfn|Stevens|1966|pp=19–20}}{{sfnm|1a1=Bullock|1a2=Orkand|1a3=Grinnell|1y=1977|1p=151|2a1=Junge|2y=1981|2pp=4–5}} At longer times, after some but not all of the ion channels have recovered, the axon can be stimulated to produce another action potential, but with a higher threshold, requiring a much stronger depolarization, e.g., to −30&nbsp;mV. The period during which action potentials are unusually difficult to evoke is called the ''relative refractory period''.{{sfn|Purves|Augustine|Fitzpatrick|Hall|2008|p=49}}{{sfn|Stevens|1966|pp=19–20}}{{sfnm|1a1=Bullock|1a2=Orkand|1a3=Grinnell|1y=1977|1p=151|2a1=Junge|2y=1981|2pp=4–5}}

===Peak phase===
The positive feedback of the rising phase slows and comes to a halt as the sodium ion channels become maximally open. At the peak of the action potential, the sodium permeability is maximized and the membrane voltage ''V<sub>m</sub>'' is nearly equal to the sodium equilibrium voltage ''E''<sub>Na</sub>. However, the same raised voltage that opened the sodium channels initially also slowly shuts them off, by closing their pores; the sodium channels become ''inactivated''.{{sfnm|1a1=Purves|1a2=Augustine|1a3=Fitzpatrick|1a4=Hall|1y=2008|1p=47|2a1=Purves|2a2=Augustine|2a3=Fitzpatrick|2a4=Hall|2y=2008|2p=65|3a1=Bullock|3a2=Orkand|3a3=Grinnell|3y=1977|3pp=147–148|4a1=Stevens|4y=1966|4p=128}} This lowers the membrane's permeability to sodium relative to potassium, driving the membrane voltage back towards the resting value. At the same time, the raised voltage opens voltage-sensitive potassium channels; the increase in the membrane's potassium permeability drives ''V<sub>m</sub>'' towards ''E''<sub>K</sub>.{{sfnm|1a1=Purves|1a2=Augustine|1a3=Fitzpatrick|1a4=Hall|1y=2008|1p=47|2a1=Purves|2a2=Augustine|2a3=Fitzpatrick|2a4=Hall|2y=2008|2p=65|3a1=Bullock|3a2=Orkand|3a3=Grinnell|3y=1977|3pp=147–148|4a1=Stevens|4y=1966|4p=128}} Combined, these changes in sodium and potassium permeability cause ''V<sub>m</sub>'' to drop quickly, repolarizing the membrane and producing the "falling phase" of the action potential.{{sfn|Purves|Augustine|Fitzpatrick|Hall|2008|p=49}}{{sfn|Bullock|Orkand|Grinnell|1977|p=152}}{{sfn|Schmidt-Nielsen|1997|pp=483–484}}{{sfnm|1a1=Bullock|1a2=Orkand|1a3=Grinnell|1y=1977|1pp=147–149|2a1=Stevens|2y=1966|2pp=126–127}}

===<!--"Afterhyperpolarization" is a single word; please do not divide it into two words!-->Afterhyperpolarization===
The depolarized voltage opens additional voltage-dependent potassium channels, and some of these do not close right away when the membrane returns to its normal resting voltage. In addition, [[SK channel|further potassium channels]] open in response to the influx of calcium ions during the action potential. The intracellular concentration of potassium ions is transiently unusually low, making the membrane voltage ''V<sub>m</sub>'' even closer to the potassium equilibrium voltage ''E''<sub>K</sub>. The membrane potential goes below the resting membrane potential. Hence, there is an undershoot or [[hyperpolarization (biology)|hyperpolarization]], termed an [[afterhyperpolarization]], that persists until the membrane potassium permeability returns to its usual value, restoring the membrane potential to the resting state.{{sfn|Purves|Augustine|Fitzpatrick|Hall|2008|p=37}}{{sfn|Bullock|Orkand|Grinnell|1977|p=152}}

===Refractory period===
Each action potential is followed by a [[refractory period (physiology)|refractory period]], which can be divided into an ''absolute refractory period'', during which it is impossible to evoke another action potential, and then a ''relative refractory period'', during which a stronger-than-usual stimulus is required.{{sfn|Purves|Augustine|Fitzpatrick|Hall|2008|p=49}}{{sfn|Stevens|1966|pp=19–20}}{{sfnm|1a1=Bullock|1a2=Orkand|1a3=Grinnell|1y=1977|1p=151|2a1=Junge|2y=1981|2pp=4–5}} These two refractory periods are caused by changes in the state of sodium and potassium channel molecules. When closing after an action potential, sodium channels enter an [[Sodium channel#Gating|"inactivated" state]], in which they cannot be made to open regardless of the membrane potential—this gives rise to the absolute refractory period. Even after a sufficient number of sodium channels have transitioned back to their resting state, it frequently happens that a fraction of potassium channels remains open, making it difficult for the membrane potential to depolarize, and thereby giving rise to the relative refractory period. Because the density and subtypes of potassium channels may differ greatly between different types of neurons, the duration of the relative refractory period is highly variable.{{cn|date=May 2024}}

The absolute refractory period is largely responsible for the unidirectional propagation of action potentials along axons.{{sfn|Purves|Augustine|Fitzpatrick|Hall|2008|p=56}} At any given moment, the patch of axon behind the actively spiking part is refractory, but the patch in front, not having been activated recently, is capable of being stimulated by the depolarization from the action potential.

==Propagation==
{{Main|Nerve conduction velocity}} <!-- note: factually not a main article, but a stub in need of expansion; perhaps the material below should simply be moved there and a summary left in its place -->

The action potential generated at the axon hillock propagates as a wave along the axon.{{sfn|Bullock|Orkand|Grinnell|1977|pp=160–164}} The currents flowing inwards at a point on the axon during an action potential spread out along the axon, and depolarize the adjacent sections of its membrane. If sufficiently strong, this depolarization provokes a similar action potential at the neighboring membrane patches. This basic mechanism was demonstrated by [[Alan Lloyd Hodgkin]] in 1937. After crushing or cooling nerve segments and thus blocking the action potentials, he showed that an action potential arriving on one side of the block could provoke another action potential on the other, provided that the blocked segment was sufficiently short.<ref group=lower-alpha>{{cite journal | vauthors = Hodgkin AL | title = Evidence for electrical transmission in nerve: Part I | journal = The Journal of Physiology | volume = 90 | issue = 2 | pages = 183–210 | date = July 1937 | pmid = 16994885 | pmc = 1395060 | doi = 10.1113/jphysiol.1937.sp003507 | author-link = Alan Lloyd Hodgkin }}<br />* {{cite journal | vauthors = Hodgkin AL | title = Evidence for electrical transmission in nerve: Part II | journal = The Journal of Physiology | volume = 90 | issue = 2 | pages = 211–32 | date = July 1937 | pmid = 16994886 | pmc = 1395062 | doi = 10.1113/jphysiol.1937.sp003508 | author-link = Alan Lloyd Hodgkin }}</ref>

Once an action potential has occurred at a patch of membrane, the membrane patch needs time to recover before it can fire again. At the molecular level, this ''absolute refractory period'' corresponds to the time required for the voltage-activated sodium channels to recover from inactivation, i.e., to return to their closed state.{{sfn|Stevens|1966|pp=19–20}} There are many types of voltage-activated potassium channels in neurons. Some of them inactivate fast (A-type currents) and some of them inactivate slowly or not inactivate at all; this variability guarantees that there will be always an available source of current for repolarization, even if some of the potassium channels are inactivated because of preceding depolarization. On the other hand, all neuronal voltage-activated sodium channels inactivate within several milliseconds during strong depolarization, thus making following depolarization impossible until a substantial fraction of sodium channels have returned to their closed state. Although it limits the frequency of firing,{{sfn|Stevens|1966|pp=21–23}} the absolute refractory period ensures that the action potential moves in only one direction along an axon.{{sfn|Purves|Augustine|Fitzpatrick|Hall|2008|p=56}} The currents flowing in due to an action potential spread out in both directions along the axon.{{sfn|Bullock|Orkand|Grinnell|1977|pp=161–164}} However, only the unfired part of the axon can respond with an action potential; the part that has just fired is unresponsive until the action potential is safely out of range and cannot restimulate that part. In the usual [[orthodromic conduction]], the action potential propagates from the axon hillock towards the synaptic knobs (the axonal termini); propagation in the opposite direction—known as [[antidromic conduction]]—is very rare.{{sfn|Bullock|Orkand|Grinnell|1977|p=509}} However, if a laboratory axon is stimulated in its middle, both halves of the axon are "fresh", i.e., unfired; then two action potentials will be generated, one traveling towards the axon hillock and the other traveling towards the synaptic knobs.

===Myelin and saltatory conduction===
{{Main|Myelination|Saltatory conduction}}
[[Image:Neuron1.jpg|thumb|In [[saltatory conduction]], an action potential at one [[node of Ranvier]] causes inwards currents that depolarize the membrane at the next node, provoking a new action potential there; the action potential appears to "hop" from node to node.|alt=Axons of neurons are wrapped by several myelin sheaths, which shield the axon from extracellular fluid. There are short gaps between the myelin sheaths known as ''nodes of Ranvier'' where the axon is directly exposed to the surrounding extracellular fluid.]]
In order to enable fast and efficient transduction of electrical signals in the nervous system, certain neuronal axons are covered with [[myelin]] sheaths. Myelin is a multilamellar membrane that enwraps the axon in segments separated by intervals known as [[nodes of Ranvier]]. It is produced by specialized cells: [[Schwann cell]]s exclusively in the [[peripheral nervous system]], and [[oligodendrocyte]]s exclusively in the [[central nervous system]]. Myelin sheath reduces membrane capacitance and increases membrane resistance in the inter-node intervals, thus allowing a fast, saltatory movement of action potentials from node to node.<ref name=Zalc group=lower-alpha>{{cite book | vauthors = Zalc B | title = Purinergic Signalling in Neuron–Glia Interactions | chapter = The Acquisition of Myelin: A Success Story | journal = Novartis Foundation Symposium | volume = 276 | pages = 15–21; discussion 21–5, 54–7, 275–81 | year = 2006 | pmid = 16805421 | doi = 10.1002/9780470032244.ch3 | isbn = 978-0-470-03224-4 | series = Novartis Foundation Symposia }}</ref><ref name="S. Poliak & E. Peles" group=lower-alpha>{{cite journal | vauthors = Poliak S, Peles E | title = The local differentiation of myelinated axons at nodes of Ranvier | journal = Nature Reviews. Neuroscience | volume = 4 | issue = 12 | pages = 968–80 | date = December 2003 | pmid = 14682359 | doi = 10.1038/nrn1253 | s2cid = 14720760 }}</ref><ref group=lower-alpha>{{cite journal | vauthors = Simons M, Trotter J | title = Wrapping it up: the cell biology of myelination | journal = Current Opinion in Neurobiology | volume = 17 | issue = 5 | pages = 533–40 | date = October 2007 | pmid = 17923405 | doi = 10.1016/j.conb.2007.08.003 | s2cid = 45470194 }}</ref> Myelination is found mainly in [[vertebrate]]s, but an analogous system has been discovered in a few invertebrates, such as some species of [[shrimp]].<ref group=lower-alpha>{{cite journal | vauthors = Xu K, Terakawa S | title = Fenestration nodes and the wide submyelinic space form the basis for the unusually fast impulse conduction of shrimp myelinated axons | journal = The Journal of Experimental Biology | volume = 202 | issue = Pt 15 | pages = 1979–89 | date = August 1999 | doi = 10.1242/jeb.202.15.1979 | pmid = 10395528 | bibcode = 1999JExpB.202.1979X | url = http://jeb.biologists.org/cgi/pmidlookup?view=long&pmid=10395528 }}</ref> Not all neurons in vertebrates are myelinated; for example, axons of the neurons comprising the autonomous nervous system are not, in general, myelinated.

Myelin prevents ions from entering or leaving the axon along myelinated segments. As a general rule, myelination increases the [[conduction velocity]] of action potentials and makes them more energy-efficient. Whether saltatory or not, the mean conduction velocity of an action potential ranges from 1&nbsp;[[Metre per second|meter per second]] (m/s) to over 100&nbsp;m/s, and, in general, increases with axonal diameter.<ref name="hursh_1939" group=lower-alpha>{{cite journal | vauthors = Hursh JB | year = 1939 | title = Conduction velocity and diameter of nerve fibers | journal = American Journal of Physiology | volume = 127 | pages = 131–39| doi = 10.1152/ajplegacy.1939.127.1.131 }}</ref>

Action potentials cannot propagate through the membrane in myelinated segments of the axon. However, the current is carried by the cytoplasm, which is sufficient to depolarize the first or second subsequent [[node of Ranvier]]. Instead, the ionic current from an action potential at one [[node of Ranvier]] provokes another action potential at the next node; this apparent "hopping" of the action potential from node to node is known as [[saltatory conduction]]. Although the mechanism of saltatory conduction was suggested in 1925 by Ralph Lillie,<ref group=lower-alpha>{{cite journal | vauthors = Lillie RS | title = Factors Affecting Transmission and Recovery in the Passive Iron Nerve Model | journal = The Journal of General Physiology | volume = 7 | issue = 4 | pages = 473–507 | date = March 1925 | pmid = 19872151 | pmc = 2140733 | doi = 10.1085/jgp.7.4.473 }} See also {{harvnb|Keynes|Aidley|1991|p=78}}</ref> the first experimental evidence for saltatory conduction came from [[Ichiji Tasaki]]<ref name="tasaki_1939" group=lower-alpha>{{cite journal | vauthors = Tasaki I | year = 1939 | title = Electro-saltatory transmission of nerve impulse and effect of narcosis upon nerve fiber | journal = Am. J. Physiol. | volume = 127 | pages = 211–27| doi = 10.1152/ajplegacy.1939.127.2.211 }}</ref> and Taiji Takeuchi<ref name="tasaki_1941_1942_1959" group=lower-alpha>{{cite journal | vauthors = Tasaki I, Takeuchi T | year = 1941 | title = Der am Ranvierschen Knoten entstehende Aktionsstrom und seine Bedeutung für die Erregungsleitung | journal = Pflügers Archiv für die gesamte Physiologie | volume = 244 | pages = 696–711 | doi = 10.1007/BF01755414 | issue = 6 | s2cid = 8628858 }}<br />* {{cite journal | vauthors = Tasaki I, Takeuchi T | year = 1942 | title = Weitere Studien über den Aktionsstrom der markhaltigen Nervenfaser und über die elektrosaltatorische Übertragung des nervenimpulses | journal = Pflügers Archiv für die gesamte Physiologie | volume = 245 | pages = 764–82 | doi = 10.1007/BF01755237 | issue = 5 | s2cid = 44315437 }}</ref><ref>Tasaki, I in {{harvnb|Field|1959|pp=75–121}}</ref> and from [[Andrew Huxley]] and Robert Stämpfli.<ref name="huxley_staempfli_1949_1951" group=lower-alpha>{{cite journal | vauthors = Huxley AF, Stämpfli R | title = Evidence for saltatory conduction in peripheral myelinated nerve fibres | journal = The Journal of Physiology | volume = 108 | issue = 3 | pages = 315–39 | date = May 1949 | pmid = 16991863 | pmc = 1392492 | doi = 10.1113/jphysiol.1949.sp004335 | author-link1 = Andrew Huxley }}<br />* {{cite journal | vauthors = Huxley AF, Stampfli R | title = Direct determination of membrane resting potential and action potential in single myelinated nerve fibers | journal = The Journal of Physiology | volume = 112 | issue = 3–4 | pages = 476–95 | date = February 1951 | pmid = 14825228 | pmc = 1393015 | doi = 10.1113/jphysiol.1951.sp004545 | author-link1 = Andrew Huxley }}</ref> By contrast, in unmyelinated axons, the action potential provokes another in the membrane immediately adjacent, and moves continuously down the axon like a wave.

[[Image:Conduction velocity and myelination.png|thumb|right|300px|Comparison of the [[conduction velocity|conduction velocities]] of myelinated and unmyelinated [[axon]]s in the [[cat]].{{sfn|Schmidt-Nielsen|1997|loc=Figure 12.13}} The conduction velocity ''v'' of myelinated neurons varies roughly linearly with axon diameter ''d'' (that is, ''v'' ∝ ''d''),<ref name="hursh_1939" group=lower-alpha /> whereas the speed of unmyelinated neurons varies roughly as the square root (''v'' ∝{{radic|''d''}}).<ref name="rushton_1951" group=lower-alpha>{{cite journal | vauthors = Rushton WA | title = A theory of the effects of fibre size in medullated nerve | journal = The Journal of Physiology | volume = 115 | issue = 1 | pages = 101–22 | date = September 1951 | pmid = 14889433 | pmc = 1392008 | doi = 10.1113/jphysiol.1951.sp004655 | author-link = W. A. H. Rushton }}</ref> The red and blue curves are fits of experimental data, whereas the dotted lines are their theoretical extrapolations.|alt=A log-log plot of conduction velocity (m/s) vs axon diameter (μm).]]

Myelin has two important advantages: fast conduction speed and energy efficiency. For axons larger than a minimum diameter (roughly 1 [[micrometre]]), myelination increases the [[conduction velocity]] of an action potential, typically tenfold.<ref name="hartline_2007" group=lower-alpha /> Conversely, for a given conduction velocity, myelinated fibers are smaller than their unmyelinated counterparts. For example, action potentials move at roughly the same speed (25&nbsp;m/s) in a myelinated frog axon and an unmyelinated [[squid giant axon]], but the frog axon has a roughly 30-fold smaller diameter and 1000-fold smaller cross-sectional area. Also, since the ionic currents are confined to the nodes of Ranvier, far fewer ions "leak" across the membrane, saving metabolic energy. This saving is a significant [[natural selection|selective advantage]], since the human nervous system uses approximately 20% of the body's metabolic energy.<ref name="hartline_2007" group=lower-alpha>{{cite journal | vauthors = Hartline DK, Colman DR | title = Rapid conduction and the evolution of giant axons and myelinated fibers | journal = Current Biology | volume = 17 | issue = 1 | pages = R29-35 | date = January 2007 | pmid = 17208176 | doi = 10.1016/j.cub.2006.11.042 | s2cid = 10033356 | doi-access = free | bibcode = 2007CBio...17R..29H }}</ref>

The length of axons' myelinated segments is important to the success of saltatory conduction. They should be as long as possible to maximize the speed of conduction, but not so long that the arriving signal is too weak to provoke an action potential at the next node of Ranvier. In nature, myelinated segments are generally long enough for the passively propagated signal to travel for at least two nodes while retaining enough amplitude to fire an action potential at the second or third node. Thus, the [[safety factor]] of saltatory conduction is high, allowing transmission to bypass nodes in case of injury. However, action potentials may end prematurely in certain places where the safety factor is low, even in unmyelinated neurons; a common example is the branch point of an axon, where it divides into two axons.{{sfn|Bullock|Orkand|Grinnell|1977|p=163}}

Some diseases degrade myelin and impair saltatory conduction, reducing the conduction velocity of action potentials.<ref group=lower-alpha>{{cite journal | vauthors = Miller RH, Mi S | title = Dissecting demyelination | journal = Nature Neuroscience | volume = 10 | issue = 11 | pages = 1351–4 | date = November 2007 | pmid = 17965654 | doi = 10.1038/nn1995 | s2cid = 12441377 }}</ref> The most well-known of these is [[multiple sclerosis]], in which the breakdown of myelin impairs coordinated movement.<ref>Waxman, SG in {{harvnb|Waxman|2007|loc=''Multiple Sclerosis as a Neurodegenerative Disease'', pp. 333–346.}}</ref>

===Cable theory===
{{Main|Cable theory}}
[[File:Cable theory Neuron RC circuit v3.svg|alt=A diagram showing the resistance and capacitance across the cell membrane of an axon. The cell membrane is divided into adjacent regions, each having its own resistance and capacitance between the cytosol and extracellular fluid across the membrane. Each of these regions is in turn connected by an intracellular circuit with a resistance.|thumb|300x300px|Cable theory's simplified view of a neuronal fiber. The connected [[RC circuit]]s correspond to adjacent segments of a passive [[neurite]]. The extracellular resistances ''r<sub>e</sub>'' (the counterparts of the intracellular resistances ''r<sub>i</sub>'') are not shown, since they are usually negligibly small; the extracellular medium may be assumed to have the same voltage everywhere.]]
The flow of currents within an axon can be described quantitatively by [[cable theory]]<ref name="rall_1989">[[Wilfrid Rall|Rall, W]] in {{harvnb|Koch|Segev|1989|loc=''Cable Theory for Dendritic Neurons'', pp. 9–62.}}</ref> and its elaborations, such as the compartmental model.<ref name="segev_1989">{{cite book | vauthors = Segev I, Fleshman JW, Burke RE | chapter = Compartmental Models of Complex Neurons | title = Methods in Neuronal Modeling: From Synapses to Networks. | veditors = Koch C, Segev I  | editor1-link = Christof Koch | date = 1989 | pages = 63–96 | publisher = The MIT Press | location = Cambridge, Massachusetts | isbn = 978-0-262-11133-1 | lccn = 88008279 | oclc = 18384545 }}</ref> Cable theory was developed in 1855 by [[William Thomson, 1st Baron Kelvin|Lord Kelvin]] to model the transatlantic telegraph cable<ref name="kelvin_1855" group=lower-alpha>{{cite journal | vauthors = Kelvin WT | year = 1855 | title = On the theory of the electric telegraph | journal = Proceedings of the Royal Society | volume = 7 | pages = 382–99 | doi = 10.1098/rspl.1854.0093| s2cid = 178547827 | author-link = William Thomson, 1st Baron Kelvin }}</ref> and was shown to be relevant to neurons by [[Alan Lloyd Hodgkin|Hodgkin]] and [[W. A. H. Rushton|Rushton]] in 1946.<ref name="hodgkin_1946" group=lower-alpha>{{cite journal | vauthors = Hodgkin AL, Rushton WA | title = The electrical constants of a crustacean nerve fibre | journal = Proceedings of the Royal Society of Medicine | volume = 134 | issue = 873 | pages = 444–79 | date = December 1946 | pmid = 20281590 | doi = 10.1098/rspb.1946.0024 | author-link1 = Alan Lloyd Hodgkin | bibcode = 1946RSPSB.133..444H | doi-access = free }}</ref> In simple cable theory, the neuron is treated as an electrically passive, perfectly cylindrical transmission cable, which can be described by a [[partial differential equation]]<ref name="rall_1989" />

:<math>
\tau \frac{\partial V}{\partial t} = \lambda^2 \frac{\partial^2 V}{\partial x^2} - V
</math>

where ''V''(''x'', ''t'') is the voltage across the membrane at a time ''t'' and a position ''x'' along the length of the neuron, and where λ and τ are the characteristic length and time scales on which those voltages decay in response to a stimulus. Referring to the circuit diagram on the right, these scales can be determined from the resistances and capacitances per unit length.{{sfn|Purves|Augustine|Fitzpatrick|Hall|2008|pp=52–53}}

:<math>
\tau =\ r_m c_m \,
</math>

:<math>
\lambda = \sqrt \frac{r_m}{r_\ell}
</math>

These time and length-scales can be used to understand the dependence of the conduction velocity on the diameter of the neuron in unmyelinated fibers. For example, the time-scale τ increases with both the membrane resistance ''r<sub>m</sub>'' and capacitance ''c<sub>m</sub>''. As the capacitance increases, more charge must be transferred to produce a given transmembrane voltage (by [[capacitance|the equation ''Q''&nbsp;=&nbsp;''CV'']]); as the resistance increases, less charge is transferred per unit time, making the equilibration slower. In a similar manner, if the internal resistance per unit length ''r<sub>i</sub>'' is lower in one axon than in another (e.g., because the radius of the former is larger), the spatial decay length λ becomes longer and the [[conduction velocity]] of an action potential should increase. If the transmembrane resistance ''r<sub>m</sub>'' is increased, that lowers the average "leakage" current across the membrane, likewise causing ''λ'' to become longer, increasing the conduction velocity.

==Termination==

===Chemical synapses===
{{Main|Chemical synapse|Neurotransmitter|Excitatory postsynaptic potential|Inhibitory postsynaptic potential}}

In general, action potentials that reach the synaptic knobs cause a [[neurotransmitter]] to be released into the synaptic cleft.<ref group=lower-alpha>{{cite book | vauthors = Süudhof TC | chapter = Neurotransmitter Release | title = Pharmacology of Neurotransmitter Release | volume = 184 | issue = 184 | pages = 1–21 | year = 2008 | pmid = 18064409 | doi = 10.1007/978-3-540-74805-2_1 | isbn = 978-3-540-74804-5 | series = Handbook of Experimental Pharmacology }}</ref> Neurotransmitters are small molecules that may open ion channels in the postsynaptic cell; most axons have the same neurotransmitter at all of their termini. The arrival of the action potential opens voltage-sensitive calcium channels in the presynaptic membrane; the influx of calcium causes [[synaptic vesicle|vesicles]] filled with neurotransmitter to migrate to the cell's surface and [[exocytosis|release their contents]] into the [[synaptic cleft]].<ref group=lower-alpha>{{cite journal | vauthors = Rusakov DA | title = Ca2+-dependent mechanisms of presynaptic control at central synapses | journal = The Neuroscientist | volume = 12 | issue = 4 | pages = 317–26 | date = August 2006 | pmid = 16840708 | pmc = 2684670 | doi = 10.1177/1073858405284672 }}</ref> This complex process is inhibited by the [[neurotoxin]]s [[tetanospasmin]] and [[botulinum toxin]], which are responsible for [[tetanus]] and [[botulism]], respectively.<ref group=lower-alpha>{{cite journal | vauthors = Humeau Y, Doussau F, Grant NJ, Poulain B | title = How botulinum and tetanus neurotoxins block neurotransmitter release | journal = Biochimie | volume = 82 | issue = 5 | pages = 427–46 | date = May 2000 | pmid = 10865130 | doi = 10.1016/S0300-9084(00)00216-9 }}</ref>

[[Image:Gap cell junction-en.svg|thumb|right|[[Electrical synapse]]s between excitable cells allow ions to pass directly from one cell to another, and are much faster than [[chemical synapse]]s.|alt=Electrical synapases are composed of protein complexes that are imbedded in both membranes of adjacent neurons and thereby provide a direct channel for ions to flow from the cytoplasm of one cell into an adjacent cell.]]

===Electrical synapses===
{{Main|Electrical synapse|Gap junction|Connexin}}

Some synapses dispense with the "middleman" of the neurotransmitter, and connect the presynaptic and postsynaptic cells together.<ref group=lower-alpha>{{cite journal | vauthors = Zoidl G, Dermietzel R | title = On the search for the electrical synapse: a glimpse at the future | journal = Cell and Tissue Research | volume = 310 | issue = 2 | pages = 137–42 | date = November 2002 | pmid = 12397368 | doi = 10.1007/s00441-002-0632-x | s2cid = 22414506 }}</ref> When an action potential reaches such a synapse, the ionic currents flowing into the presynaptic cell can cross the barrier of the two cell membranes and enter the postsynaptic cell through pores known as [[connexon]]s.<ref group=lower-alpha>{{cite journal | vauthors = Brink PR, Cronin K, Ramanan SV | title = Gap junctions in excitable cells | journal = Journal of Bioenergetics and Biomembranes | volume = 28 | issue = 4 | pages = 351–8 | date = August 1996 | pmid = 8844332 | doi = 10.1007/BF02110111 | s2cid = 46371790 }}</ref> Thus, the ionic currents of the presynaptic action potential can directly stimulate the postsynaptic cell. Electrical synapses allow for faster transmission because they do not require the slow diffusion of [[neurotransmitter]]s across the synaptic cleft. Hence, electrical synapses are used whenever fast response and coordination of timing are crucial, as in [[escape reflex]]es, the [[retina]] of [[vertebrate]]s, and the [[heart]].

===Neuromuscular junctions===
{{Main|Neuromuscular junction|Acetylcholine receptor|Cholinesterase enzyme}}

A special case of a chemical synapse is the [[neuromuscular junction]], in which the [[axon]] of a [[motor neuron]] terminates on a [[muscle fiber]].<ref group=lower-alpha>{{cite journal | vauthors = Hirsch NP | title = Neuromuscular junction in health and disease | journal = British Journal of Anaesthesia | volume = 99 | issue = 1 | pages = 132–8 | date = July 2007 | pmid = 17573397 | doi = 10.1093/bja/aem144 | df = dmy-all | doi-access = free }}</ref> In such cases, the released neurotransmitter is [[acetylcholine]], which binds to the acetylcholine receptor, an integral membrane protein in the membrane (the ''[[sarcolemma]]'') of the muscle fiber.<ref group=lower-alpha>{{cite journal | vauthors = Hughes BW, Kusner LL, Kaminski HJ | title = Molecular architecture of the neuromuscular junction | journal = Muscle & Nerve | volume = 33 | issue = 4 | pages = 445–61 | date = April 2006 | pmid = 16228970 | doi = 10.1002/mus.20440 | s2cid = 1888352 }}</ref> However, the acetylcholine does not remain bound; rather, it dissociates and is [[hydrolysis|hydrolyzed]] by the enzyme, [[acetylcholinesterase]], located in the synapse. This enzyme quickly reduces the stimulus to the muscle, which allows the degree and timing of muscular contraction to be regulated delicately. Some poisons inactivate acetylcholinesterase to prevent this control, such as the [[nerve agent]]s [[sarin]] and [[tabun (nerve agent)|tabun]],<ref name=Newmark group=lower-alpha>{{cite journal | vauthors = Newmark J | title = Nerve agents | journal = The Neurologist | volume = 13 | issue = 1 | pages = 20–32 | date = January 2007 | pmid = 17215724 | doi = 10.1097/01.nrl.0000252923.04894.53 | s2cid = 211234081 }}</ref> and the insecticides [[diazinon]] and [[malathion]].<ref group=lower-alpha>{{cite journal | vauthors = Costa LG | title = Current issues in organophosphate toxicology | journal = Clinica Chimica Acta; International Journal of Clinical Chemistry | volume = 366 | issue = 1–2 | pages = 1–13 | date = April 2006 | pmid = 16337171 | doi = 10.1016/j.cca.2005.10.008 }}</ref>

==Other cell types==

===Cardiac action potentials===
{{Main|Cardiac action potential|Electrical conduction system of the heart|Cardiac pacemaker|Heart arrhythmia}}

[[Image:Ventricular myocyte action potential.svg|thumb|right|220px|Phases of a cardiac action potential. The sharp rise in voltage ("0") corresponds to the influx of sodium ions, whereas the two decays ("1" and "3", respectively) correspond to the sodium-channel inactivation and the repolarizing eflux of potassium ions. The characteristic plateau ("2") results from the opening of voltage-sensitive [[calcium]] channels.|alt=Plot of membrane potential versus time. The initial resting phase (region 4) is negative and constant flowed by sharp rise (0) to a peak (1). The plateau phase (2) is slightly below the peak. The plateau phase is followed by a fairly rapid return (3) back to the resting potential (4).]]

The cardiac action potential differs from the neuronal action potential by having an extended plateau, in which the membrane is held at a high voltage for a few hundred milliseconds prior to being repolarized by the potassium current as usual.<ref name=Kleber group=lower-alpha /> This plateau is due to the action of slower [[calcium]] channels opening and holding the membrane voltage near their equilibrium potential even after the sodium channels have inactivated.

The cardiac action potential plays an important role in coordinating the contraction of the heart.<ref name=Kleber group=lower-alpha>{{cite journal | vauthors = Kléber AG, Rudy Y | title = Basic mechanisms of cardiac impulse propagation and associated arrhythmias | journal = Physiological Reviews | volume = 84 | issue = 2 | pages = 431–88 | date = April 2004 | pmid = 15044680 | doi = 10.1152/physrev.00025.2003 | s2cid = 21823003 }}</ref> The cardiac cells of the [[sinoatrial node]] provide the [[pacemaker potential]] that synchronizes the heart. The action potentials of those cells propagate to and through the [[atrioventricular node]] (AV node), which is normally the only conduction pathway between the [[atrium (heart)|atria]] and the [[ventricle (heart)|ventricles]]. Action potentials from the AV node travel through the [[bundle of His]] and thence to the [[Purkinje fiber]]s.<ref group=note>These [[Purkinje fiber]]s are muscle fibers and not related to the [[Purkinje cell]]s, which are [[neuron]]s found in the [[cerebellum]].</ref> Conversely, anomalies in the cardiac action potential—whether due to a congenital mutation or injury—can lead to human pathologies, especially [[Heart arrhythmia|arrhythmia]]s.<ref name=Kleber group=lower-alpha /> Several anti-arrhythmia drugs act on the cardiac action potential, such as [[quinidine]], [[lidocaine]], [[beta blocker]]s, and [[verapamil]].<ref group=lower-alpha>{{cite journal | vauthors = Tamargo J, Caballero R, Delpón E | title = Pharmacological approaches in the treatment of atrial fibrillation | journal = Current Medicinal Chemistry | volume = 11 | issue = 1 | pages = 13–28 | date = January 2004 | pmid = 14754423 | doi = 10.2174/0929867043456241 }}</ref>

===Muscular action potentials===
{{Main|Neuromuscular junction|Muscle contraction}}

The action potential in a normal skeletal muscle cell is similar to the action potential in neurons.{{sfn|Ganong|1991|pp=59–60}} Action potentials result from the depolarization of the cell membrane (the [[sarcolemma]]), which opens voltage-sensitive sodium channels; these become inactivated and the membrane is repolarized through the outward current of potassium ions. The resting potential prior to the action potential is typically −90mV, somewhat more negative than typical neurons. The muscle action potential lasts roughly 2–4&nbsp;ms, the absolute refractory period is roughly 1–3&nbsp;ms, and the conduction velocity along the muscle is roughly 5&nbsp;m/s. The action potential releases [[calcium]] ions that free up the [[tropomyosin]] and allow the muscle to contract. Muscle action potentials are provoked by the arrival of a pre-synaptic neuronal action potential at the [[neuromuscular junction]], which is a common target for [[neurotoxin]]s.<ref name=Newmark group=lower-alpha />

===Plant action potentials===
{{See also|Variation potential}}

[[Plant cells|Plant]] and [[fungi|fungal cells]]<ref name="Slayman_1976" group=lower-alpha>{{cite journal | vauthors = Slayman CL, Long WS, Gradmann D | title = "Action potentials" in Neurospora crassa, a mycelial fungus | journal = Biochimica et Biophysica Acta (BBA) - Biomembranes | volume = 426 | issue = 4 | pages = 732–44 | date = April 1976 | pmid = 130926 | doi = 10.1016/0005-2736(76)90138-3 }}</ref> are also electrically excitable. The fundamental difference from animal action potentials is that the depolarization in plant cells is not accomplished by an uptake of positive sodium ions, but by release of negative ''chloride'' ions.<ref name = "Mummert_1991" group=lower-alpha>{{cite journal | vauthors = Mummert H, Gradmann D | title = Action potentials in Acetabularia: measurement and simulation of voltage-gated fluxes | journal = The Journal of Membrane Biology | volume = 124 | issue = 3 | pages = 265–73 | date = December 1991 | pmid = 1664861 | doi = 10.1007/BF01994359 | s2cid = 22063907 }}</ref><ref name = "Gradmann_2001" group=lower-alpha>{{cite journal | vauthors = Gradmann D | year = 2001 | title = Models for oscillations in plants | journal = Aust. J. Plant Physiol. | volume = 28 | issue = 7 | pages = 577–590 | doi = 10.1071/pp01017}}</ref><ref name = "Beilby_2007" group=lower-alpha>{{cite book | vauthors = Beilby MJ | title = Action Potential in Charophytes | volume = 257 | pages = 43–82 | year = 2007 | pmid = 17280895 | doi = 10.1016/S0074-7696(07)57002-6 | isbn = 978-0-12-373701-4 | series = International Review of Cytology }}</ref> In 1906, J. C. Bose published the first measurements of action potentials in plants, which had previously been discovered by Burdon-Sanderson and Darwin.<ref>{{Cite journal|last=Tandon|first=Prakash N|date=2019-07-01|title=Jagdish Chandra Bose and Plant Neurobiology: Part I|url=http://insa.nic.in/writereaddata/UpLoadedFiles/IJHS/Vol54_2_2019__Art05.pdf|journal=Indian Journal of History of Science|volume=54|issue=2|doi=10.16943/ijhs/2019/v54i2/49660|issn=0019-5235|doi-access=free}}</ref> An increase in cytoplasmic calcium ions may be the cause of anion release into the cell. This makes calcium a precursor to ion movements, such as the influx of negative chloride ions and efflux of positive potassium ions, as seen in barley leaves.<ref>{{cite journal | vauthors = Felle HH, Zimmermann MR | title = Systemic signalling in barley through action potentials | journal = Planta | volume = 226 | issue = 1 | pages = 203–14 | date = June 2007 | pmid = 17226028 | doi = 10.1007/s00425-006-0458-y | bibcode = 2007Plant.226..203F | s2cid = 5059716 }}</ref>

The initial influx of calcium ions also poses a small cellular depolarization, causing the voltage-gated ion channels to open and allowing full depolarization to be propagated by chloride ions.

Some plants (e.g. ''[[Dionaea muscipula]]'') use sodium-gated channels to operate plant movements and "count" stimulation events to determine if a threshold for movement is met. ''Dionaea muscipula'', also known as the Venus flytrap, is found in subtropical wetlands in North and South Carolina.<ref>{{Cite journal|last=Luken|first=James O. | name-list-style = vanc |date= December 2005 |title=Habitats of Dionaea muscipula (Venus' Fly Trap), Droseraceae, Associated with Carolina Bays|journal=Southeastern Naturalist|language=en|volume=4|issue=4|pages=573–584|doi=10.1656/1528-7092(2005)004[0573:HODMVF]2.0.CO;2|s2cid=9246114 |issn=1528-7092}}</ref> When there are poor soil nutrients, the flytrap relies on a diet of insects and animals.<ref name=":1">{{cite journal | vauthors = Böhm J, Scherzer S, Krol E, Kreuzer I, von Meyer K, Lorey C, Mueller TD, Shabala L, Monte I, Solano R, Al-Rasheid KA, Rennenberg H, Shabala S, Neher E, Hedrich R | display-authors = 6 | title = The Venus Flytrap Dionaea muscipula Counts Prey-Induced Action Potentials to Induce Sodium Uptake | journal = Current Biology | volume = 26 | issue = 3 | pages = 286–95 | date = February 2016 | pmid = 26804557 | pmc = 4751343 | doi = 10.1016/j.cub.2015.11.057 | bibcode = 2016CBio...26..286B }}</ref> Despite research on the plant, there lacks an understanding behind the molecular basis to the Venus flytraps, and carnivore plants in general.<ref name=":2">{{cite journal | vauthors = Hedrich R, Neher E | title = Venus Flytrap: How an Excitable, Carnivorous Plant Works | journal = Trends in Plant Science | volume = 23 | issue = 3 | pages = 220–234 | date = March 2018 | pmid = 29336976 | doi = 10.1016/j.tplants.2017.12.004 | bibcode = 2018TPS....23..220H }}</ref>

However, plenty of research has been done on action potentials and how they affect movement and clockwork within the Venus flytrap. To start, the resting membrane potential of the Venus flytrap (−120&nbsp;mV) is lower than animal cells (usually −90&nbsp;mV to −40&nbsp;mV).<ref name=":2" /><ref>Purves D, Augustine GJ, Fitzpatrick D, et al., editors. Neuroscience. 2nd edition. Sunderland (MA): Sinauer Associates; 2001. Electrical Potentials Across Nerve Cell Membranes. Available from: [https://www.ncbi.nlm.nih.gov/books/NBK11069/]</ref> The lower resting potential makes it easier to activate an action potential. Thus, when an insect lands on the trap of the plant, it triggers a hair-like mechanoreceptor.<ref name=":2" /> This receptor then activates an action potential that lasts around 1.5&nbsp;ms.<ref>{{cite journal | vauthors = Volkov AG, Adesina T, Jovanov E | title = Closing of venus flytrap by electrical stimulation of motor cells | journal = Plant Signaling & Behavior | volume = 2 | issue = 3 | pages = 139–45 | date = May 2007 | pmid = 19516982 | pmc = 2634039 | doi = 10.4161/psb.2.3.4217 | bibcode = 2007PlSiB...2..139V }}</ref> This causes an increase of positive calcium ions into the cell, slightly depolarizing it. However, the flytrap does not close after one trigger. Instead, it requires the activation of two or more hairs.<ref name=":1" /><ref name=":2" /> If only one hair is triggered, it disregards the activation as a false positive. Further, the second hair must be activated within a certain time interval (0.75–40&nbsp;s) for it to register with the first activation.<ref name=":2" /> Thus, a buildup of calcium begins and then slowly falls after the first trigger. When the second action potential is fired within the time interval, it reaches the calcium threshold to depolarize the cell, closing the trap on the prey within a fraction of a second.<ref name=":2" />

Together with the subsequent release of positive potassium ions the action potential in plants involves an [[osmotic]] loss of salt (KCl). Whereas, the animal action potential is osmotically neutral because equal amounts of entering sodium and leaving potassium cancel each other osmotically. The interaction of electrical and osmotic relations in plant cells<ref name="Gradmann_1998" group="lower-alpha">{{cite journal | vauthors = Gradmann D, Hoffstadt J | title = Electrocoupling of ion transporters in plants: interaction with internal ion concentrations | journal = The Journal of Membrane Biology | volume = 166 | issue = 1 | pages = 51–9 | date = November 1998 | pmid = 9784585 | doi = 10.1007/s002329900446 | s2cid = 24190001 }}</ref> appears to have arisen from an osmotic function of electrical excitability in a common unicellular ancestors of plants and animals under changing salinity conditions. Further, the present function of rapid signal transmission is seen as a newer accomplishment of [[metazoan]] cells in a more stable osmotic environment.<ref name="Gradmann_1980">
Gradmann, D; Mummert, H in {{harvnb|Spanswick|Lucas|Dainty|1980|loc=''Plant action potentials'', pp. 333–344.}}</ref> It is likely that the familiar signaling function of action potentials in some vascular plants (e.g. ''[[Mimosa pudica]]'') arose independently from that in metazoan excitable cells.

Unlike the rising phase and peak, the falling phase and after-hyperpolarization seem to depend primarily on cations that are not calcium. To initiate repolarization, the cell requires movement of potassium out of the cell through passive transportation on the membrane. This differs from neurons because the movement of potassium does not dominate the decrease in membrane potential. To fully repolarize, a plant cell requires energy in the form of ATP to assist in the release of hydrogen from the cell – utilizing a transporter called [[proton ATPase]].<ref name="Opritov">Opritov, V A, et al. "Direct Coupling of Action Potential Generation in Cells of a Higher Plant (Cucurbita Pepo) with the Operation of an Electrogenic Pump." ''Russian Journal of Plant Physiology'', vol. 49, no. 1, 2002, pp. 142–147.</ref><ref name=":2" />

==Taxonomic distribution and evolutionary advantages==
Action potentials are found throughout [[multicellular organism]]s, including [[plant]]s, [[invertebrate]]s such as [[insect]]s, and [[vertebrate]]s such as [[reptile]]s and [[mammal]]s.<ref name=Fromm group=lower-alpha>{{cite journal | vauthors = Fromm J, Lautner S | title = Electrical signals and their physiological significance in plants | journal = Plant, Cell & Environment | volume = 30 | issue = 3 | pages = 249–257 | date = March 2007 | pmid = 17263772 | doi = 10.1111/j.1365-3040.2006.01614.x | doi-access = free | bibcode = 2007PCEnv..30..249F }}</ref> [[Sponge]]s seem to be the main [[phylum]] of multicellular [[eukaryote]]s that does not transmit action potentials, although some studies have suggested that these organisms have a form of electrical signaling, too.<ref group=lower-alpha>{{cite journal | vauthors = Leys SP, Mackie GO, Meech RW | title = Impulse conduction in a sponge | journal = The Journal of Experimental Biology | volume = 202 (Pt 9) | issue = 9 | pages = 1139–50 | date = May 1999 | doi = 10.1242/jeb.202.9.1139 | pmid = 10101111 | bibcode = 1999JExpB.202.1139L | url = http://jeb.biologists.org/cgi/pmidlookup?view=long&pmid=10101111 }}</ref> The resting potential, as well as the size and duration of the action potential, have not varied much with evolution, although the [[conduction velocity]] does vary dramatically with axonal diameter and myelination.

{| class="wikitable" id="action_potential_texonomic_comparison" align="center"
|+ Comparison of action potentials (APs) from a representative cross-section of animals{{sfn|Bullock|Horridge|1965}}
! Animal !! Cell type !! Resting potential (mV) !! AP increase (mV) !! AP duration (ms) !! Conduction speed (m/s)
|-
| Squid (''Loligo'') || Giant axon || −60 || 120 || 0.75 || 35
|-
| Earthworm (''Lumbricus'') || Median giant fiber || −70 || 100 || 1.0 || 30
|-
| Cockroach (''Periplaneta'') || Giant fiber || −70 || 80–104 || 0.4 || 10
|-
| Frog (''Rana'') || Sciatic nerve axon || −60 to −80 || 110–130 || 1.0 || 7–30
|-
| Cat (''Felis'') || Spinal motor neuron || −55 to −80 || 80–110 || 1–1.5 || 30–120
|}

Given its conservation throughout evolution, the action potential seems to confer evolutionary advantages. One function of action potentials is rapid, long-range signaling within the organism; the conduction velocity can exceed 110&nbsp;m/s, which is one-third the [[speed of sound]]. For comparison, a hormone molecule carried in the bloodstream moves at roughly 8&nbsp;m/s in large arteries. Part of this function is the tight coordination of mechanical events, such as the contraction of the heart. A second function is the computation associated with its generation. Being an all-or-none signal that does not decay with transmission distance, the action potential has similar advantages to [[digital electronics]]. The integration of various dendritic signals at the axon hillock and its thresholding to form a complex train of action potentials is another form of computation, one that has been exploited biologically to form [[central pattern generator]]s and mimicked in [[artificial neural network]]s.

The common prokaryotic/eukaryotic ancestor, which lived perhaps four billion years ago, is believed to have had voltage-gated channels. This functionality was likely, at some later point, cross-purposed to provide a communication mechanism. Even modern single-celled bacteria can utilize action potentials to communicate with other bacteria in the same [[biofilm]].<ref>{{cite journal | vauthors = Kristan WB | title = Early evolution of neurons | journal = Current Biology | volume = 26 | issue = 20 | pages = R949–R954 | date = October 2016 | pmid = 27780067 | doi = 10.1016/j.cub.2016.05.030 | doi-access = free | bibcode = 2016CBio...26.R949K }}</ref>

==Experimental methods==
{{See also|Electrophysiology}}

[[Image:Loligo forbesii.jpg|thumb|right|250px|Giant axons of the longfin inshore squid (''[[Doryteuthis pealeii]]'') were [[Marine Biological Laboratory#Neuroscience, neurobiology, and sensory physiology|crucial for scientists]] to understand the action potential.<ref>{{cite book |url=https://books.google.com/books?id=SDi2BQAAQBAJ |title=The Brain, the Nervous System, and Their Diseases |first=Jennifer L. |last=Hellier | name-list-style = vanc |year=2014 |pages=532 |publisher=ABC-Clio |isbn=9781610693387}}</ref>|alt=Illustration of the longfin inshore squid.]]

The study of action potentials has required the development of new experimental methods. The initial work, prior to 1955, was carried out primarily by [[Alan Lloyd Hodgkin]] and [[Andrew Fielding Huxley]], who were, along [[John Carew Eccles]], awarded the 1963 [[Nobel Prize in Physiology or Medicine]] for their contribution to the description of the ionic basis of nerve conduction. It focused on three goals: isolating signals from single neurons or axons, developing fast, sensitive electronics, and shrinking [[electrode]]s enough that the voltage inside a single cell could be recorded.

The first problem was solved by studying the [[Squid giant axon|giant axons]] found in the neurons of the [[squid]] (''[[Loligo forbesii]]'' and ''[[Doryteuthis pealeii]]'', at the time classified as ''Loligo pealeii'').<ref name="keynes_1989" group=lower-alpha>{{cite journal | vauthors = Keynes RD | title = The role of giant axons in studies of the nerve impulse | journal = BioEssays | volume = 10 | issue = 2–3 | pages = 90–3 | year = 1989 | pmid = 2541698 | doi = 10.1002/bies.950100213 }}</ref> These axons are so large in diameter (roughly 1&nbsp;mm, or 100-fold larger than a typical neuron) that they can be seen with the naked eye, making them easy to extract and manipulate.<ref name="hodgkin_1952" group=lower-alpha /><ref name=Meunier group=lower-alpha>{{cite journal | vauthors = Meunier C, Segev I | title = Playing the devil's advocate: is the Hodgkin-Huxley model useful? | journal = Trends in Neurosciences | volume = 25 | issue = 11 | pages = 558–63 | date = November 2002 | pmid = 12392930 | doi = 10.1016/S0166-2236(02)02278-6 | s2cid = 1355280 }}</ref> However, they are not representative of all excitable cells, and numerous other systems with action potentials have been studied.

The second problem was addressed with the crucial development of the [[voltage clamp]],<ref name="cole_1949" group=lower-alpha>{{cite journal | vauthors = Cole KS | year = 1949 | title = Dynamic electrical characteristics of the squid axon membrane | journal = Arch. Sci. Physiol. | volume = 3 | pages = 253–8| author-link = Kenneth Stewart Cole }}</ref> which permitted experimenters to study the ionic currents underlying an action potential in isolation, and eliminated a key source of [[electronic noise]], the current ''I<sub>C</sub>'' associated with the [[capacitance]] ''C'' of the membrane.{{sfn|Junge|1981|pp=63–82}} Since the current equals ''C'' times the rate of change of the transmembrane voltage ''V<sub>m</sub>'', the solution was to design a circuit that kept ''V<sub>m</sub>'' fixed (zero rate of change) regardless of the currents flowing across the membrane. Thus, the current required to keep ''V<sub>m</sub>'' at a fixed value is a direct reflection of the current flowing through the membrane. Other electronic advances included the use of [[Faraday cage]]s and electronics with high [[input impedance]], so that the measurement itself did not affect the voltage being measured.{{sfn|Kettenmann|Grantyn|1992}}

The third problem, that of obtaining electrodes small enough to record voltages within a single axon without perturbing it, was solved in 1949 with the invention of the glass micropipette electrode,<ref name="ling_1949" group=lower-alpha>{{cite journal | vauthors = Ling G, Gerard RW | title = The normal membrane potential of frog sartorius fibers | journal = Journal of Cellular and Comparative Physiology | volume = 34 | issue = 3 | pages = 383–96 | date = December 1949 | pmid = 15410483 | doi = 10.1002/jcp.1030340304 }}</ref> which was quickly adopted by other researchers.<ref name="nastuk_1950" group=lower-alpha>{{cite journal | vauthors = Nastuk WL, Hodgkin A | year = 1950 | title = The electrical activity of single muscle fibers | journal = Journal of Cellular and Comparative Physiology | volume = 35 | pages = 39–73 | doi = 10.1002/jcp.1030350105 }}</ref><ref name="brock_1952" group=lower-alpha>{{cite journal | vauthors = Brock LG, Coombs JS, Eccles JC | title = The recording of potentials from motoneurones with an intracellular electrode | journal = The Journal of Physiology | volume = 117 | issue = 4 | pages = 431–60 | date = August 1952 | pmid = 12991232 | pmc = 1392415 | doi = 10.1113/jphysiol.1952.sp004759 }}</ref> Refinements of this method are able to produce electrode tips that are as fine as 100 [[Ångström|Å]] (10 [[nanometre|nm]]), which also confers high input impedance.<ref>Snell, FM in {{harvnb|Lavallée|Schanne|Hébert|1969|loc=''Some Electrical Properties of Fine-Tipped Pipette Microelectrodes''.}}</ref> Action potentials may also be recorded with small metal electrodes placed just next to a neuron, with [[neurochip]]s containing [[EOSFET]]s, or optically with dyes that are [[Calcium imaging|sensitive to Ca<sup>2+</sup>]] or to voltage.<ref name="dyes" group=lower-alpha>{{cite journal | vauthors = Ross WN, Salzberg BM, Cohen LB, Davila HV | title = A large change in dye absorption during the action potential | journal = Biophysical Journal | volume = 14 | issue = 12 | pages = 983–6 | date = December 1974 | pmid = 4429774 | pmc = 1334592 | doi = 10.1016/S0006-3495(74)85963-1 | bibcode = 1974BpJ....14..983R }}<br />* {{cite journal | vauthors = Grynkiewicz G, Poenie M, Tsien RY | title = A new generation of Ca2+ indicators with greatly improved fluorescence properties | journal = The Journal of Biological Chemistry | volume = 260 | issue = 6 | pages = 3440–50 | date = March 1985 | doi = 10.1016/S0021-9258(19)83641-4 | pmid = 3838314 | doi-access = free }}</ref>

[[Image:Single channel.png|thumb|left|As revealed by a [[patch clamp]] electrode, an [[ion channel]] has two states: open (high conductance) and closed (low conductance).|alt=Plot of membrane potential versus time. The channel is primarily in a high conductance state punctuated by random and relatively brief transitions to a low conductance states ]]

While glass micropipette electrodes measure the sum of the currents passing through many ion channels, studying the electrical properties of a single ion channel became possible in the 1970s with the development of the [[patch clamp]] by [[Erwin Neher]] and [[Bert Sakmann]]. For this discovery, they were awarded the [[Nobel Prize in Physiology or Medicine]] in 1991.<ref name="Nobel_1991" group=lower-Greek>{{cite press release | url = http://nobelprize.org/nobel_prizes/medicine/laureates/1991/press.html | title = The Nobel Prize in Physiology or Medicine 1991 | publisher = The Royal Swedish Academy of Science | year = 1991 | access-date = 2010-02-21 | url-status = live | archive-url = https://web.archive.org/web/20100324031907/http://nobelprize.org/nobel_prizes/medicine/laureates/1991/press.html | archive-date = 24 March 2010 | df = dmy-all }}</ref> Patch-clamping verified that ionic channels have discrete states of conductance, such as open, closed and inactivated.

[[Optical imaging]] technologies have been developed in recent years to measure action potentials, either via simultaneous multisite recordings or with ultra-spatial resolution. Using [[Potentiometric dyes|voltage-sensitive dyes]], action potentials have been optically recorded from a tiny patch of [[cardiomyocyte]] membrane.<ref name="pmid19289075" group=lower-alpha>{{cite journal | vauthors = Bu G, Adams H, Berbari EJ, Rubart M | title = Uniform action potential repolarization within the sarcolemma of in situ ventricular cardiomyocytes | journal = Biophysical Journal | volume = 96 | issue = 6 | pages = 2532–46 | date = March 2009 | pmid = 19289075 | pmc = 2907679 | doi = 10.1016/j.bpj.2008.12.3896 | bibcode = 2009BpJ....96.2532B }}</ref>

==Neurotoxins==
[[Image:Puffer Fish DSC01257.JPG|thumb|right|[[Tetrodotoxin]] is a lethal toxin found in [[pufferfish]] that inhibits the [[voltage-gated ion channel|voltage-sensitive sodium channel]], halting action potentials.|alt=Photograph of a pufferfish.]]

Several [[neurotoxin]]s, both natural and synthetic, function by blocking the action potential. [[Tetrodotoxin]] from the [[pufferfish]] and [[saxitoxin]] from the ''[[Gonyaulax]]'' (the [[dinoflagellate]] genus responsible for "[[Paralytic shellfish poisoning|red tide]]s") block action potentials by inhibiting the voltage-sensitive sodium channel;<ref name="TTX_refs" group=lower-alpha>{{cite journal | vauthors = Milligan JV, Edwards C | title = Some factors affecting the time course of the recovery of contracture ability following a potassium contracture in frog striated muscle | journal = The Journal of General Physiology | volume = 48 | issue = 6 | pages = 975–83 | date = July 1965 | pmid = 5855511 | pmc = 2195447 | doi = 10.1085/jgp.48.6.975 }}<br />* {{cite book | vauthors = Ritchie JM, Rogart RB | title = Reviews of Physiology, Biochemistry and Pharmacology, Volume 79 | chapter = The binding of saxitoxin and tetrodotoxin to excitable tissue | volume = 79 | pages = 1–50 | year = 1977 | pmid = 335473 | doi = 10.1007/BFb0037088 | isbn = 0-387-08326-X }}<br />* {{cite journal | vauthors = Keynes RD, Ritchie JM | title = On the binding of labelled saxitoxin to the squid giant axon | journal = Proceedings of the Royal Society of London. Series B, Biological Sciences | volume = 222 | issue = 1227 | pages = 147–53 | date = August 1984 | pmid = 6148754 | doi = 10.1098/rspb.1984.0055 | bibcode = 1984RSPSB.222..147K | s2cid = 11465181 }}</ref> similarly, [[dendrotoxin]] from the [[mamba|black mamba]] snake inhibits the voltage-sensitive potassium channel. Such inhibitors of ion channels serve an important research purpose, by allowing scientists to "turn off" specific channels at will, thus isolating the other channels' contributions; they can also be useful in purifying ion channels by [[affinity chromatography]] or in assaying their concentration. However, such inhibitors also make effective neurotoxins, and have been considered for use as [[Chemical warfare|chemical weapon]]s. Neurotoxins aimed at the ion channels of insects have been effective [[insecticide]]s; one example is the synthetic [[permethrin]], which prolongs the activation of the sodium channels involved in action potentials. The ion channels of insects are sufficiently different from their human counterparts that there are few side effects in humans.

==History==
[[Image:PurkinjeCell.jpg|thumb|left|Image of two [[Purkinje cell]]s (labeled as '''A''') drawn by [[Santiago Ramón y Cajal]] in 1899. Large trees of [[dendrite]]s feed into the [[soma (biology)|soma]], from which a single [[axon]] emerges and moves generally downwards with a few branch points. The smaller cells labeled '''B''' are [[granule cell]]s.|alt=Hand drawn figure of two Purkinje cells side by side with dendrites projecting upwards that look like tree branches and a few axons projected downwards that connect to a few granule cells at the bottom of the drawing.]]

The role of electricity in the nervous systems of animals was first observed in dissected [[frog]]s by [[Luigi Galvani]], who studied it from 1791 to 1797.<ref name="piccolino_1997" group=lower-alpha>{{cite journal | vauthors = Piccolino M | title = Luigi Galvani and animal electricity: two centuries after the foundation of electrophysiology | journal = Trends in Neurosciences | volume = 20 | issue = 10 | pages = 443–8 | date = October 1997 | pmid = 9347609 | doi = 10.1016/S0166-2236(97)01101-6 | s2cid = 23394494 }}</ref> Galvani's results inspired [[Alessandro Volta]] to develop the [[Voltaic pile]]—the earliest-known [[battery (electricity)|electric battery]]—with which he studied animal electricity (such as [[electric eel]]s) and the physiological responses to applied [[direct current|direct-current]] [[voltage]]s.<ref name="piccolino_2000" group=lower-alpha>{{cite journal | vauthors = Piccolino M | title = The bicentennial of the Voltaic battery (1800-2000): the artificial electric organ | journal = Trends in Neurosciences | volume = 23 | issue = 4 | pages = 147–51 | date = April 2000 | pmid = 10717671 | doi = 10.1016/S0166-2236(99)01544-1 | s2cid = 393323 }}</ref>

In the 19th century scientists studied the propagation of electrical signals in whole [[nerve]]s (i.e., bundles of [[neuron]]s) and demonstrated that nervous tissue was made up of [[cell (biology)|cells]], instead of an interconnected network of tubes (a ''reticulum'').{{sfnm|1a1=Brazier|1y=1961|2a1=McHenry|2a2=Garrison|2y=1969|3a1=Worden|3a2=Swazey|3a3=Adelman|3y=1975}} [[Carlo Matteucci]] followed up Galvani's studies and demonstrated that injured nerves and muscles in frogs could produce [[direct current]]. Matteucci's work inspired the German physiologist, [[Emil du Bois-Reymond]], who discovered in 1843 that stimulating these muscle and nerve preparations produced a notable diminution in their resting currents, making him the first researcher to identify the electrical nature of the action potential.<ref>{{Cite book|title=Emil du Bois-Reymond : neuroscience, self, and society in nineteenth-century Germany|last=Finkelstein | first = Gabriel Ward | name-list-style = vanc |isbn=9781461950325|location=Cambridge, Massachusetts|oclc=864592470|year = 2013}}</ref> The [[conduction velocity]] of action potentials was then measured in 1850 by du Bois-Reymond's friend, [[Hermann von Helmholtz]].<ref>[[Kathryn Olesko|Olesko, Kathryn M.]], and Frederic L. Holmes. "Experiment, Quantification and Discovery: Helmholtz's Early Physiological Researches, 1843-50". In ''Hermann von Helmholtz and the Foundations of Nineteenth Century Science'', ed. David Cahan, 50-108. Berkeley; Los Angeles; London: University of California, 1994.</ref> Progress in electrophysiology stagnated thereafter due to the limitations of chemical theory and experimental practice. To establish that nervous tissue is made up of discrete cells, the Spanish physician [[Santiago Ramón y Cajal]] and his students used a stain developed by [[Camillo Golgi]] to reveal the myriad shapes of neurons, which they rendered painstakingly. For their discoveries, Golgi and Ramón y Cajal were awarded the 1906 [[Nobel Prize in Physiology or Medicine|Nobel Prize in Physiology]].<ref name="Nobel_1906" group=lower-Greek>{{cite press release | url = http://nobelprize.org/medicine/laureates/1906/index.html | title = The Nobel Prize in Physiology or Medicine 1906 | publisher = The Royal Swedish Academy of Science | year = 1906 | access-date = 2010-02-21 | url-status = live | archive-url = https://web.archive.org/web/20081204190959/http://nobelprize.org/medicine/laureates/1906/index.html | archive-date = 4 December 2008 | df = dmy-all }}</ref> Their work resolved a long-standing controversy in the [[neuroanatomy]] of the 19th century; Golgi himself had argued for the network model of the nervous system.

[[Image:3b8e.png|thumb|right|[[Ribbon diagram]] of the sodium–potassium pump in its E2-Pi state. The estimated boundaries of the [[lipid bilayer]] are shown as blue (intracellular) and red (extracellular) planes.|alt=Cartoon diagram of the sodium–potassium pump drawn vertically imbedded in a schematic diagram of a lipid bilayer represented by two parallel horizontal lines. The portion of the protein that is imbedded in the lipid bilayer is composed largely of anti-parallel beta sheets. There is also a large intracellular domain of the protein with a mixed alpha-helix/beta-sheet structure.]]

The 20th century saw significant breakthroughs in electrophysiology. In 1902 and again in 1912, [[Julius Bernstein]] advanced the hypothesis that the action potential resulted from a change in the [[permeation|permeability]] of the axonal membrane to ions.<ref name="bernstein_1902_1912" group=lower-alpha>{{cite journal | vauthors = Bernstein J | year = 1902 | title = Untersuchungen zur Thermodynamik der bioelektrischen Ströme | journal = Pflügers Archiv für die gesamte Physiologie | volume = 92 | pages = 521–562 | doi = 10.1007/BF01790181 | issue = 10–12| s2cid = 33229139 | author-link = Julius Bernstein | url = https://zenodo.org/record/2192363 }}</ref>{{sfn|Bernstein|1912}} Bernstein's hypothesis was confirmed by [[Kenneth Stewart Cole|Ken Cole]] and Howard Curtis, who showed that membrane conductance increases during an action potential.<ref group=lower-alpha>{{cite journal | vauthors = Cole KS, Curtis HJ | title = Electric Impedance of the Squid Giant Axon During Activity | journal = The Journal of General Physiology | volume = 22 | issue = 5 | pages = 649–70 | date = May 1939 | pmid = 19873125 | pmc = 2142006 | doi = 10.1085/jgp.22.5.649 | author-link1 = Kenneth Stewart Cole }}</ref> In 1907, [[Louis Lapicque]] suggested that the action potential was generated as a threshold was crossed,<ref group=lower-alpha>{{cite journal | vauthors = Lapicque L | year = 1907 | title = Recherches quantitatives sur l'excitationelectrique des nerfs traitee comme une polarisation | journal = J. Physiol. Pathol. Gen | volume = 9| pages = 620–635 }}</ref> what would be later shown as a product of the [[dynamical system]]s of ionic conductances. In 1949, [[Alan Lloyd Hodgkin|Alan Hodgkin]] and [[Bernard Katz]] refined Bernstein's hypothesis by considering that the axonal membrane might have different permeabilities to different ions; in particular, they demonstrated the crucial role of the sodium permeability for the action potential.<ref name="hodgkin_1949" group=lower-alpha>{{cite journal | vauthors = Hodgkin AL, Katz B | title = The effect of sodium ions on the electrical activity of giant axon of the squid | journal = The Journal of Physiology | volume = 108 | issue = 1 | pages = 37–77 | date = March 1949 | pmid = 18128147 | pmc = 1392331 | doi = 10.1113/jphysiol.1949.sp004310 | author-link1 = Alan Lloyd Hodgkin | author-link2 = Bernard Katz }}</ref> They made the first actual recording of the electrical changes across the neuronal membrane that mediate the action potential.<ref group=lower-Greek>{{cite journal |last=Warlow|first=Charles| name-list-style = vanc |title=The Recent Evolution of a Symbiotic Ion Channel in the Legume Family Altered Ion Conductance and Improved Functionality in Calcium Signaling|journal=Practical Neurology|volume=7|issue=3|pages=192–197|url=http://pn.bmj.com/content/7/3/192.full|publisher=BMJ Publishing Group|access-date=23 March 2013|url-status=live|archive-url=https://web.archive.org/web/20120314104408/http://pn.bmj.com/content/7/3/192.full|archive-date=14 March 2012|df=dmy-all|date=June 2007}}</ref> This line of research culminated in the five 1952 papers of Hodgkin, Katz and [[Andrew Huxley]], in which they applied the [[voltage clamp]] technique to determine the dependence of the axonal membrane's permeabilities to sodium and potassium ions on voltage and time, from which they were able to reconstruct the action potential quantitatively.<ref name="hodgkin_1952" group=lower-alpha>{{cite journal | vauthors = Hodgkin AL, Huxley AF, Katz B | title = Measurement of current-voltage relations in the membrane of the giant axon of Loligo | journal = The Journal of Physiology | volume = 116 | issue = 4 | pages = 424–48 | date = April 1952 | pmid = 14946712 | pmc = 1392219 | doi = 10.1113/jphysiol.1952.sp004716 | author-link1 = Alan Lloyd Hodgkin | author-link3 = Bernard Katz }}<br />* {{cite journal | vauthors = Hodgkin AL, Huxley AF | title = Currents carried by sodium and potassium ions through the membrane of the giant axon of Loligo | journal = The Journal of Physiology | volume = 116 | issue = 4 | pages = 449–72 | date = April 1952 | pmid = 14946713 | pmc = 1392213 | doi = 10.1113/jphysiol.1952.sp004717 | author-link1 = Alan Lloyd Hodgkin }}<br />* {{cite journal | vauthors = Hodgkin AL, Huxley AF | title = The components of membrane conductance in the giant axon of Loligo | journal = The Journal of Physiology | volume = 116 | issue = 4 | pages = 473–96 | date = April 1952 | pmid = 14946714 | pmc = 1392209 | doi = 10.1113/jphysiol.1952.sp004718 | author-link1 = Alan Lloyd Hodgkin }}<br />* {{cite journal | vauthors = Hodgkin AL, Huxley AF | title = The dual effect of membrane potential on sodium conductance in the giant axon of Loligo | journal = The Journal of Physiology | volume = 116 | issue = 4 | pages = 497–506 | date = April 1952 | pmid = 14946715 | pmc = 1392212 | doi = 10.1113/jphysiol.1952.sp004719 | author-link1 = Alan Lloyd Hodgkin }}<br />* {{cite journal | vauthors = Hodgkin AL, Huxley AF | title = A quantitative description of membrane current and its application to conduction and excitation in nerve | journal = The Journal of Physiology | volume = 117 | issue = 4 | pages = 500–44 | date = August 1952 | pmid = 12991237 | pmc = 1392413 | doi = 10.1113/jphysiol.1952.sp004764 | author-link1 = Alan Lloyd Hodgkin }}</ref> Hodgkin and Huxley correlated the properties of their mathematical model with discrete [[ion channel]]s that could exist in several different states, including "open", "closed", and "inactivated". Their hypotheses were confirmed in the mid-1970s and 1980s by [[Erwin Neher]] and [[Bert Sakmann]], who developed the technique of [[patch clamp]]ing to examine the conductance states of individual ion channels.<ref name="patch_clamp" group=lower-alpha>{{cite journal | vauthors = Neher E, Sakmann B | title = Single-channel currents recorded from membrane of denervated frog muscle fibres | journal = Nature | volume = 260 | issue = 5554 | pages = 799–802 | date = April 1976 | pmid = 1083489 | doi = 10.1038/260799a0 | author-link1 = Erwin Neher | bibcode = 1976Natur.260..799N | s2cid = 4204985 }}<br />* {{cite journal | vauthors = Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ | title = Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches | journal = Pflügers Archiv | volume = 391 | issue = 2 | pages = 85–100 | date = August 1981 | pmid = 6270629 | doi = 10.1007/BF00656997 | s2cid = 12014433 }}<br />* {{cite journal | vauthors = Neher E, Sakmann B | title = The patch clamp technique | journal = Scientific American | volume = 266 | issue = 3 | pages = 44–51 | date = March 1992 | pmid = 1374932 | doi = 10.1038/scientificamerican0392-44 | author-link1 = Erwin Neher | bibcode = 1992SciAm.266c..44N }}</ref> In the 21st century, researchers are beginning to understand the structural basis for these conductance states and for the selectivity of channels for their species of ion,<ref name="yellen_2002" group=lower-alpha>{{cite journal | vauthors = Yellen G | title = The voltage-gated potassium channels and their relatives | journal = Nature | volume = 419 | issue = 6902 | pages = 35–42 | date = September 2002 | pmid = 12214225 | doi = 10.1038/nature00978 | bibcode = 2002Natur.419...35Y | s2cid = 4420877 }}</ref> through the atomic-resolution [[X-ray crystallography|crystal structures]],<ref name="doyle_1998" group=lower-alpha>{{cite journal | vauthors = Doyle DA, Morais Cabral J, Pfuetzner RA, Kuo A, Gulbis JM, Cohen SL, Chait BT, MacKinnon R | display-authors = 6 | title = The structure of the potassium channel: molecular basis of K+ conduction and selectivity | journal = Science | volume = 280 | issue = 5360 | pages = 69–77 | date = April 1998 | pmid = 9525859 | doi = 10.1126/science.280.5360.69 | bibcode = 1998Sci...280...69D }}<br />* {{cite journal | vauthors = Zhou Y, Morais-Cabral JH, Kaufman A, MacKinnon R | title = Chemistry of ion coordination and hydration revealed by a K+ channel-Fab complex at 2.0 A resolution | journal = Nature | volume = 414 | issue = 6859 | pages = 43–8 | date = November 2001 | pmid = 11689936 | doi = 10.1038/35102009 | bibcode = 2001Natur.414...43Z | s2cid = 205022645 }}<br />* {{cite journal | vauthors = Jiang Y, Lee A, Chen J, Ruta V, Cadene M, Chait BT, MacKinnon R | title = X-ray structure of a voltage-dependent K+ channel | journal = Nature | volume = 423 | issue = 6935 | pages = 33–41 | date = May 2003 | pmid = 12721618 | doi = 10.1038/nature01580 | bibcode = 2003Natur.423...33J | s2cid = 4347957 }}</ref> fluorescence distance measurements<ref name="FRET" group=lower-alpha >{{cite journal | vauthors = Cha A, Snyder GE, Selvin PR, Bezanilla F | title = Atomic scale movement of the voltage-sensing region in a potassium channel measured via spectroscopy | journal = Nature | volume = 402 | issue = 6763 | pages = 809–13 | date = December 1999 | pmid = 10617201 | doi = 10.1038/45552 | bibcode = 1999Natur.402..809C | s2cid = 4353978 | doi-access = free }}<br />* {{cite journal | vauthors = Glauner KS, Mannuzzu LM, Gandhi CS, Isacoff EY | title = Spectroscopic mapping of voltage sensor movement in the Shaker potassium channel | journal = Nature | volume = 402 | issue = 6763 | pages = 813–7 | date = December 1999 | pmid = 10617202 | doi = 10.1038/45561 | bibcode = 1999Natur.402..813G | s2cid = 4417476 }}<br />* {{cite journal | vauthors = Bezanilla F | title = The voltage sensor in voltage-dependent ion channels | journal = Physiological Reviews | volume = 80 | issue = 2 | pages = 555–92 | date = April 2000 | pmid = 10747201 | doi = 10.1152/physrev.2000.80.2.555 | s2cid = 18629998 }}</ref> and [[cryo-electron microscopy]] studies.<ref name="cryoEM" group=lower-alpha>{{cite journal | vauthors = Catterall WA | title = A 3D view of sodium channels | journal = Nature | volume = 409 | issue = 6823 | pages = 988–9, 991 | date = February 2001 | pmid = 11234048 | doi = 10.1038/35059188 | bibcode = 2001Natur.409..988C | s2cid = 4371677 | doi-access = free }}<br />* {{cite journal | vauthors = Sato C, Ueno Y, Asai K, Takahashi K, Sato M, Engel A, Fujiyoshi Y | title = The voltage-sensitive sodium channel is a bell-shaped molecule with several cavities | journal = Nature | volume = 409 | issue = 6823 | pages = 1047–51 | date = February 2001 | pmid = 11234014 | doi = 10.1038/35059098 | bibcode = 2001Natur.409.1047S | s2cid = 4430165 }}</ref>

Julius Bernstein was also the first to introduce the [[Nernst equation]] for [[resting potential]] across the membrane; this was generalized by [[David E. Goldman]] to the eponymous [[Goldman equation]] in 1943.<ref name="goldman_1943" group=lower-alpha>{{cite journal | vauthors = Goldman DE | title = Potential, Impedance, and Rectification in Membranes | journal = The Journal of General Physiology | volume = 27 | issue = 1 | pages = 37–60 | date = September 1943 | pmid = 19873371 | pmc = 2142582 | doi = 10.1085/jgp.27.1.37 }}</ref> The [[sodium–potassium pump]] was identified in 1957<ref group=lower-alpha>{{cite journal | vauthors = Skou JC | title = The influence of some cations on an adenosine triphosphatase from peripheral nerves | journal = Biochimica et Biophysica Acta | volume = 23 | issue = 2 | pages = 394–401 | date = February 1957 | pmid = 13412736 | doi = 10.1016/0006-3002(57)90343-8 | s2cid = 32516710 }}</ref><ref group=lower-Greek>{{cite press release | url = http://nobelprize.org/nobel_prizes/medicine/laureates/1997/press.html | title = The Nobel Prize in Chemistry 1997 | publisher = The Royal Swedish Academy of Science | year = 1997 | access-date = 2010-02-21 | url-status = live | archive-url = https://web.archive.org/web/20091023003257/http://nobelprize.org/nobel_prizes/medicine/laureates/1997/press.html | archive-date = 23 October 2009 | df = dmy-all }}</ref> and its properties gradually elucidated,<ref name="hodgkin_1955" group=lower-alpha>{{cite journal | vauthors = Hodgkin AL, Keynes RD | title = Active transport of cations in giant axons from Sepia and Loligo | journal = The Journal of Physiology | volume = 128 | issue = 1 | pages = 28–60 | date = April 1955 | pmid = 14368574 | pmc = 1365754 | doi = 10.1113/jphysiol.1955.sp005290 | author-link1 = Alan Lloyd Hodgkin }}</ref><ref name="caldwell_1960" group=lower-alpha>{{cite journal | vauthors = Caldwell PC, Hodgkin AL, Keynes RD, Shaw TL | title = The effects of injecting 'energy-rich' phosphate compounds on the active transport of ions in the giant axons of Loligo | journal = The Journal of Physiology | volume = 152 | issue = 3 | pages = 561–90 | date = July 1960 | pmid = 13806926 | pmc = 1363339 | doi = 10.1113/jphysiol.1960.sp006509 }}</ref><ref name="caldwell_1957" group=lower-alpha>{{cite journal | vauthors = Caldwell PC, Keynes RD | title = The utilization of phosphate bond energy for sodium extrusion from giant axons | journal = The Journal of Physiology | volume = 137 | issue = 1 | pages = 12–3P | date = June 1957 | pmid = 13439598 | doi = 10.1113/jphysiol.1957.sp005830 | s2cid = 222188054 }}</ref> culminating in the determination of its atomic-resolution structure by [[X-ray crystallography]].<ref name="Na_K_pump_structure" group=lower-alpha>{{cite journal | vauthors = Morth JP, Pedersen BP, Toustrup-Jensen MS, Sørensen TL, Petersen J, Andersen JP, Vilsen B, Nissen P | display-authors = 6 | title = Crystal structure of the sodium-potassium pump | journal = Nature | volume = 450 | issue = 7172 | pages = 1043–9 | date = December 2007 | pmid = 18075585 | doi = 10.1038/nature06419 | bibcode = 2007Natur.450.1043M | s2cid = 4344526 }}</ref> The crystal structures of related ionic pumps have also been solved, giving a broader view of how these [[molecular machine]]s work.<ref group=lower-alpha>{{cite journal | vauthors = Lee AG, East JM | title = What the structure of a calcium pump tells us about its mechanism | journal = The Biochemical Journal | volume = 356 | issue = Pt 3 | pages = 665–83 | date = June 2001 | pmid = 11389676 | pmc = 1221895 | doi = 10.1042/0264-6021:3560665 }}</ref>

==Quantitative models==
{{Main|Quantitative models of the action potential}}

[[Image:MembraneCircuit.svg|thumb|336px|right|Equivalent electrical circuit for the Hodgkin–Huxley model of the action potential. ''I<sub>m</sub>'' and ''V<sub>m</sub>'' represent the current through, and the voltage across, a small patch of membrane, respectively. The ''C<sub>m</sub>'' represents the capacitance of the membrane patch, whereas the four ''g''{{'s}} represent the [[electrical conductance|conductances]] of four types of ions. The two conductances on the left, for potassium (K) and sodium (Na), are shown with arrows to indicate that they can vary with the applied voltage, corresponding to the [[voltage-gated ion channel|voltage-sensitive ion channels]]. The two conductances on the right help determine the [[resting membrane potential]].|alt=Circuit diagram depicting five parallel circuits that are interconnected at the top to the extracellular solution and at the bottom to the intracellular solution.]]

Mathematical and computational models are essential for understanding the action potential, and offer predictions that may be tested against experimental data, providing a stringent test of a theory. The most important and accurate of the early neural models is the [[Hodgkin–Huxley model]], which describes the action potential by a coupled set of four [[ordinary differential equation]]s (ODEs).<ref name="hodgkin_1952" group=lower-alpha /> Although the Hodgkin–Huxley model may be a simplification with few limitations<ref>{{cite journal | vauthors = Baranauskas G, Martina M | title = Sodium currents activate without a Hodgkin-and-Huxley-type delay in central mammalian neurons | journal = The Journal of Neuroscience | volume = 26 | issue = 2 | pages = 671–84 | date = January 2006 | pmid = 16407565 | pmc = 6674426 | doi = 10.1523/jneurosci.2283-05.2006 }}</ref> compared to the realistic nervous membrane as it exists in nature, its complexity has inspired several even-more-simplified models,{{sfn|Hoppensteadt|1986}}<ref group=lower-alpha>* {{cite journal | vauthors = Fitzhugh R | title = Thresholds and plateaus in the Hodgkin-Huxley nerve equations | journal = The Journal of General Physiology | volume = 43 | issue = 5 | pages = 867–96 | date = May 1960 | pmid = 13823315 | pmc = 2195039 | doi = 10.1085/jgp.43.5.867 }}<br />* {{cite journal | vauthors = Kepler TB, Abbott LF, Marder E | title = Reduction of conductance-based neuron models | journal = Biological Cybernetics | volume = 66 | issue = 5 | pages = 381–7 | year = 1992 | pmid = 1562643 | doi = 10.1007/BF00197717 | s2cid = 6789007 }}</ref> such as the [[Morris–Lecar model]]<ref name="morris_1981" group=lower-alpha>{{cite journal | vauthors = Morris C, Lecar H | title = Voltage oscillations in the barnacle giant muscle fiber | journal = Biophysical Journal | volume = 35 | issue = 1 | pages = 193–213 | date = July 1981 | pmid = 7260316 | pmc = 1327511 | doi = 10.1016/S0006-3495(81)84782-0 | bibcode = 1981BpJ....35..193M }}</ref> and the [[FitzHugh–Nagumo model]],<ref name="fitzhugh" group=lower-alpha>{{cite journal | vauthors = Fitzhugh R | title = Impulses and Physiological States in Theoretical Models of Nerve Membrane | journal = Biophysical Journal | volume = 1 | issue = 6 | pages = 445–66 | date = July 1961 | pmid = 19431309 | pmc = 1366333 | doi = 10.1016/S0006-3495(61)86902-6 | bibcode = 1961BpJ.....1..445F }}<br />* {{cite journal | vauthors = Nagumo J, Arimoto S, Yoshizawa S | year = 1962 | title = An active pulse transmission line simulating nerve axon | journal = Proceedings of the IRE | volume = 50 | pages = 2061–2070 | doi = 10.1109/JRPROC.1962.288235 | issue = 10 | s2cid = 51648050 }}</ref> both of which have only two coupled ODEs. The properties of the Hodgkin–Huxley and FitzHugh–Nagumo models and their relatives, such as the Bonhoeffer–Van der Pol model,<ref name="bonhoeffer_vanderPol" group=lower-alpha>{{cite journal | vauthors = Bonhoeffer KF | title = Activation of passive iron as a model for the excitation of nerve | journal = The Journal of General Physiology | volume = 32 | issue = 1 | pages = 69–91 | date = September 1948 | pmid = 18885679 | pmc = 2213747 | doi = 10.1085/jgp.32.1.69 }}<br />* {{cite journal | vauthors = Bonhoeffer KF | year = 1953 | title = Modelle der Nervenerregung | journal = Naturwissenschaften | volume = 40 | pages = 301–311 | doi = 10.1007/BF00632438|bibcode = 1953NW.....40..301B | issue = 11 | s2cid = 19149460 }}<br />* {{cite journal | vauthors = Van der Pol B | year = 1926 | title = On relaxation-oscillations | journal = Philosophical Magazine | volume = 2 | pages = 977–992| author-link = Balthasar van der Pol }}<br />* {{cite journal | year = 1928 | title = The heartbeat considered as a relaxation oscillation, and an electrical model of the heart | journal = Philosophical Magazine | volume = 6 | pages = 763–775| vauthors = Van der Pol B, Van der Mark J| author-link1 = Balthasar van der Pol | doi=10.1080/14786441108564652}}<br />* {{cite journal | year = 1929 | title = The heartbeat considered as a relaxation oscillation, and an electrical model of the heart | journal = Arch. Neerl. Physiol. | volume = 14 | pages = 418–443| vauthors = Van der Pol B, van der Mark J| author-link1 = Balthasar van der Pol }}</ref> have been well-studied within mathematics,<ref name="math_studies">Sato, S; Fukai, H; Nomura, T; Doi, S in {{harvnb|Reeke|Poznanski|Sporns|Rosenberg|2005|loc=''Bifurcation Analysis of the Hodgkin-Huxley Equations'', pp. 459–478.}}<br />* FitzHugh, R in {{harvnb|Schwann|1969|loc=''Mathematical models of axcitation and propagation in nerve'', pp. 12–16.}}<br />* {{harvnb|Guckenheimer|Holmes|1986|pp=12–16}}</ref><ref group=lower-alpha>{{cite journal | vauthors = Evans JW | year = 1972 | title = Nerve axon equations. I. Linear approximations | journal = Indiana Univ. Math. J. | volume = 21 | pages = 877–885 | doi = 10.1512/iumj.1972.21.21071 | issue = 9| doi-access = free }}<br />* {{cite journal | vauthors = Evans JW, Feroe J | year = 1977 | title = Local stability theory of the nerve impulse | journal = Math. Biosci. | volume = 37 | pages = 23–50 | doi = 10.1016/0025-5564(77)90076-1 }}</ref> computation<ref name="computational_studies">Nelson, ME; Rinzel, J in {{harvnb|Bower|Beeman|1995|loc=''The Hodgkin-Huxley Model'', pp. 29–49.}}<br />* Rinzel, J & Ermentrout, GB; in {{harvnb|Koch|Segev|1989|loc=''Analysis of Neural Excitability and Oscillations'', pp. 135–169.}}</ref> and electronics.<ref name="keener_1983" group=lower-alpha>{{cite journal | vauthors = Keener JP | year = 1983 | title = Analogue circuitry for the Van der Pol and FitzHugh-Nagumo equations | journal = IEEE Transactions on Systems, Man, and Cybernetics | volume = 13 | issue = 5 | pages = 1010–1014 | doi = 10.1109/TSMC.1983.6313098 | s2cid = 20077648 }}</ref> However the simple models of generator potential and action potential fail to accurately reproduce the near threshold neural spike rate and spike shape, specifically for the [[mechanoreceptors]] like the [[Pacinian corpuscle]].<ref>{{cite journal | vauthors = Biswas A, Manivannan M, Srinivasan MA | title = Vibrotactile sensitivity threshold: nonlinear stochastic mechanotransduction model of the Pacinian Corpuscle | journal = IEEE Transactions on Haptics | volume = 8 | issue = 1 | pages = 102–13 | year = 2015 | pmid = 25398183 | doi = 10.1109/TOH.2014.2369422 | s2cid = 15326972 | url = https://zenodo.org/record/894772 }}</ref> More modern research has focused on larger and more integrated systems; by joining action-potential models with models of other parts of the nervous system (such as dendrites and synapses), researchers can study [[neural computation]]{{sfnm|1a1=McCulloch|1y=1988|1pp=19–39, 46–66, 72–141|2a1=Anderson|2a2=Rosenfeld|2y=1988|2pp=15–41}} and simple [[reflex]]es, such as [[escape reflex]]es and others controlled by [[central pattern generator]]s.<ref name="cpg">Getting, PA in {{harvnb|Koch|Segev|1989|loc=''Reconstruction of Small Neural Networks'', pp. 171–194.}}</ref><ref name="pmid10713861" group=lower-alpha>{{cite journal | vauthors = Hooper SL | title = Central pattern generators | journal = Current Biology | volume = 10 | issue = 5 | pages = R176–R179 | date = March 2000 | pmid = 10713861 | doi = 10.1016/S0960-9822(00)00367-5 | bibcode = 2000CBio...10.R176H | citeseerx = 10.1.1.133.3378 | s2cid = 11388348 }}</ref>
{{Clear}}

== See also ==
{{col div|colwidth=40em}}
* [[Anode break excitation]]
* [[Bioelectricity]]
* [[Biological neuron model]]
* [[Bursting]]
* [[Central pattern generator]]
* [[Chronaxie]]
* [[Frog battery]]
* [[Law of specific nerve energies]]
* [[Neural accommodation]]
* [[Single-unit recording]]
* [[Soliton model in neuroscience]]
{{colend}}

==Notes==
<references group=note/>

== References ==
===Footnotes===
{{Reflist|32em}}

===Journal articles===
{{Reflist|group=lower-alpha|2}}

===Books===
{{Refbegin|32em}}
* {{cite book | veditors = Anderson JA, Rosenfeld E |year = 1988 |title = Neurocomputing: Foundations of Research |publisher = The MIT Press |location = Cambridge, Massachusetts |isbn = 978-0-262-01097-9 |lccn = 87003022 |oclc = 15860311 |url-access = registration |url = https://archive.org/details/neurocomputingfo0000unse }}
* {{cite book | vauthors = Bernstein J | author-link1 = Julius Bernstein | year = 1912 | title = Elektrobiologie, die Lehre von den elektrischen Vorgängen im Organismus auf moderner Grundlage dargestellt | trans-title = Electric Biology, the study of the electrical processes in the organism represented on a modern basis | publisher = Vieweg und Sohn | location = Braunschweig | lccn = 12027986 | oclc = 11358569 }}
* {{cite book | vauthors = Bower JM, Beeman D | year = 1995 | title = The Book of GENESIS: Exploring Realistic Neural Models with the GEneral NEural SImulation System | publisher = TELOS | location = Santa Clara, Calif. | isbn = 978-0-387-94019-9 | lccn = 94017624 | oclc = 30518469 }}
* {{cite book | vauthors = Brazier MA | year = 1961 | title = A History of the Electrical Activity of the Brain | publisher = Pitman | location = London | lccn = 62001407 | oclc = 556863 }}
* {{cite book | vauthors = Bullock TH, Horridge GA | author-link1 = Theodore Holmes Bullock | year = 1965 | title = Structure and Function in the Nervous Systems of Invertebrates | url = https://archive.org/details/structurefunctio0000bull | url-access = registration | series = A series of books in biology | publisher = W. H. Freeman | location = San Francisco | lccn = 65007965 | oclc = 558128 }}
* {{cite book | vauthors = Bullock TH, Orkand R, Grinnell A | author-link1 = Theodore Holmes Bullock  | year = 1977 | title = Introduction to Nervous Systems | url = https://archive.org/details/introductiontone00theo | url-access = registration | series = A series of books in biology | publisher = W. H. Freeman | location = San Francisco | isbn = 978-0-7167-0030-2 | lccn = 76003735 | oclc = 2048177 }}
* {{cite book | veditors = Field J |date=1959 | title = Handbook of Physiology: a Critical, Comprehensive Presentation of Physiological Knowledge and Concepts: Section 1: Neurophysiology | volume = 1 | publisher = American Physiological Society | location = Washington, DC | lccn = 60004587 | oclc = 830755894 }}
* {{cite book | first1 = WF | last1 = Ganong | year = 1991 | title = Review of Medical Physiology | journal = Ganong's Review of Medical Physiology | edition = 15th | publisher = Appleton and Lange | location = Norwalk, Conn. | isbn = 978-0-8385-8418-7 | lccn = 87642343 | oclc = 23761261 | issn = 0892-1253 }}
* {{cite book | veditors = Guckenheimer J, Holmes P | year = 1986 | title = Nonlinear Oscillations, Dynamical Systems and Bifurcations of Vector Fields | edition = 2nd | series = Applied Mathematical Sciences | volume = 42 | publisher = Springer Verlag | location = New York | isbn = 978-0-387-90819-9 | oclc = 751129941 }}
* {{cite book | vauthors = Hoppensteadt FC | year = 1986 | title = An Introduction to the Mathematics of Neurons | series = Cambridge studies in mathematical biology | volume = 6 | publisher = Cambridge University Press | location = Cambridge | isbn = 978-0-521-31574-6 | lccn = 85011013 | oclc = 12052275 }}
* {{cite book | vauthors = Junge D |year = 1981 |title = Nerve and Muscle Excitation |edition = 2nd |publisher = Sinauer Associates |location = Sunderland, Mass. |isbn = 978-0-87893-410-2 |lccn = 80018158 |oclc = 6486925 |url = https://archive.org/details/nervemuscleexcit00jung }}
* {{cite book | veditors = Kettenmann H, Grantyn R | year = 1992 | title = Practical Electrophysiological Methods: A Guide for in Vitro Studies in Vertebrate Neurobiology | publisher = Wiley | location = New York | isbn = 978-0-471-56200-9 | lccn = 92000179 | oclc = 25204689 }}
* {{cite book | vauthors = Keynes RD, Aidley DJ | author-link1 = Richard Keynes | year = 1991 | title = Nerve and Muscle | edition = 2nd | publisher = Cambridge University Press | location = Cambridge | isbn = 978-0-521-41042-7 | lccn = 90015167 | oclc = 25204483 }}
* {{cite book | veditors = Koch C, Segev I | editor1-link = Christof Koch | year = 1989 | title = Methods in Neuronal Modeling: From Synapses to Networks | publisher = The MIT Press | location = Cambridge, Massachusetts | isbn = 978-0-262-11133-1 | lccn = 88008279 | oclc = 18384545 }}
* {{cite book | veditors = Lavallée M, Schanne OF, Hébert NC | year = 1969 | title = Glass Microelectrodes | publisher = Wiley | location = New York | isbn = 978-0-471-51885-3 | lccn = 68009252 | oclc = 686 }}
* {{cite book | vauthors = McCulloch WS | author-link1 = Warren Sturgis McCulloch | year = 1988 | title = Embodiments of Mind | publisher = The MIT Press | location = Cambridge, Massachusetts | isbn = 978-0-262-63114-3 | lccn = 88002987 | oclc = 237280 }}
* {{cite book | vauthors = McHenry LC, Garrison FH | year = 1969 | title = Garrison's History of Neurology | publisher = Charles C. Thomas | location = Springfield, Ill. | oclc = 429733931 }}
* {{cite book | vauthors = Silverthorn DU | year = 2010 | title = Human Physiology: An Integrated Approach | edition = 5th | publisher = Pearson | location = San Francisco | isbn = 978-0-321-55980-7 | lccn = 2008050369 | oclc = 268788623 }}
* {{cite book | veditors = Spanswick RM, Lucas WJ, Dainty J | year = 1980 | title = Plant Membrane Transport: Current Conceptual Issues | series = Developments in Plant Biology | volume = 4 | publisher = Elsevier Biomedical Press | location = Amsterdam | isbn = 978-0-444-80192-0 | lccn = 79025719 | oclc = 5799924 }}
* {{cite book | vauthors = Purves D, Augustine GJ, Fitzpatrick D, Hall WC, Lamantia AS, McNamara JO, Williams SM | year = 2001 | title = Neuroscience | edition = 2nd | publisher = Sinauer Associates | location = Sunderland, MA | chapter = Release of Transmitters from Synaptic Vesicles | chapter-url = https://www.ncbi.nlm.nih.gov/books/bv.fcgi?rid=neurosci.section.326 | isbn = 978-0-87893-742-4 | lccn = 00059496 | oclc = 806472664 }}
* {{cite book | vauthors = Purves D, Augustine GJ, Fitzpatrick D, Hall WC, Lamantia AS, McNamara JO, White LE | year = 2008 | title = Neuroscience | edition = 4th | publisher = Sinauer Associates | location = Sunderland, MA | isbn = 978-0-87893-697-7 | lccn = 2007024950 | oclc = 144771764 }}
* {{cite book | veditors = Reeke GN, Poznanski RR, Sporns O, Rosenberg JR, Lindsay KA | year = 2005 | title = Modeling in the Neurosciences: from Biological Systems to Neuromimetic Robotics | publisher = Taylor & Francis | location = Boca Raton, Fla. | isbn = 978-0-415-32868-5 | lccn = 2005298022 | oclc = 489024131 }}
* {{cite book | vauthors = Schmidt-Nielsen K | author-link1 = Knut Schmidt-Nielsen | year = 1997 | title = Animal Physiology: Adaptation and Environment | edition = 5th | publisher = Cambridge University Press | location = Cambridge | isbn = 978-0-521-57098-5 | lccn = 96039295 | oclc = 35744403 }}
* {{cite book | veditors = Schwann HP | year = 1969 | title = Biological Engineering | series = Inter-University Electronics Series | volume = 9 | publisher = McGraw-Hill | location = New York | isbn = 978-0-07-055734-5 | lccn = 68027513 | oclc = 51993 }}
* {{cite book | vauthors = Stevens CF | year = 1966 | title = Neurophysiology: A Primer | url = https://archive.org/details/neurophysiologyp0000stev | url-access = registration | publisher = John Wiley and Sons | location = New York | isbn = 9780471824367 | lccn = 66015872 | oclc = 1175605 }}
* {{cite book | veditors = Waxman SG | year = 2007 | title = Molecular Neurology | publisher = Elsevier Academic Press | location = Burlington, Mass. | isbn = 978-0-12-369509-3 | lccn = 2008357317 | oclc = 154760295 }}
* {{cite book | veditors = Worden FG, Swazey JP, Adelman G | year = 1975 | title = The Neurosciences, Paths of Discovery | publisher = The MIT Press | location = Cambridge, Massachusetts | isbn = 978-0-262-23072-8 | lccn = 75016379 | oclc = 1500233 | url = https://archive.org/details/TheNeurosc_00_Word }}
{{Refend}}

===Web pages===
{{Reflist|group=lower-Greek|32em}}

== Further reading ==
{{Refbegin|32em}}
* {{cite book |vauthors=Aidley DJ, Stanfield PR | year = 1996 | title = Ion Channels: Molecules in Action | publisher = Cambridge University Press | location = Cambridge | isbn = 978-0-521-49882-1}}
* {{cite book |vauthors=Bear MF, Connors BW, Paradiso MA | year = 2001 | title = Neuroscience: Exploring the Brain | publisher = Lippincott | location = Baltimore | isbn = 0-7817-3944-6}}
* {{cite journal | vauthors = Clay JR | title = Axonal excitability revisited | journal = Progress in Biophysics and Molecular Biology | volume = 88 | issue = 1 | pages = 59–90 | date = May 2005 | pmid = 15561301 | doi = 10.1016/j.pbiomolbio.2003.12.004 | url = https://zenodo.org/record/1259297 | doi-access = free }}
* {{cite book | year = 1987 | title = Neuroelectric Systems | publisher = New York University Press | location = New York | isbn = 0-8147-1782-9| vauthors = Deutsch S, Micheli-Tzanakou E | author-link2 = Evangelia Micheli-Tzanakou }}
* {{cite book | vauthors = Hille B | year = 2001 | title = Ion Channels of Excitable Membranes | edition = 3rd | publisher = Sinauer Associates | location = Sunderland, MA | isbn = 978-0-87893-321-1| author-link = Bertil Hille }}
* {{cite book | vauthors = Johnston D, Wu SM | year = 1995 | title = Foundations of Cellular Neurophysiology | publisher = Bradford Book, The MIT Press | location = Cambridge, Massachusetts | isbn = 0-262-10053-3}}
* {{cite book | year = 2000 | title = Principles of Neural Science | edition = 4th | publisher = McGraw-Hill | location = New York | isbn = 0-8385-7701-6 |vauthors= Kandel ER, Schwartz JH, Jessell TM | author-link1 = Eric R. Kandel | title-link = Principles of Neural Science }}
* {{cite book | author = Miller C | year = 1987 | chapter = How ion channel proteins work | title = Neuromodulation: The Biochemical Control of Neuronal Excitability | veditors = Kaczmarek LK, Levitan IB | publisher = Oxford University Press | location = New York | isbn = 978-0-19-504097-5 | pages = 39–63}}
* {{cite book | vauthors = Nelson DL, Cox MM | year = 2008 | title = Lehninger Principles of Biochemistry | edition = 5th | publisher = W. H. Freeman | location = New York | isbn = 978-0-7167-7108-1 | url = https://archive.org/details/lehningerprincip00lehn_1 }}
{{Refend}}

== External links ==
{{Spoken Wikipedia|Action_potential.ogg|date=2005-06-22}}
* [https://web.archive.org/web/20050625075706/http://www.blackwellpublishing.com/matthews/channel.html Ionic flow in action potentials] at [[Blackwell Publishing]]
* [https://web.archive.org/web/20070615135508/http://www.blackwellpublishing.com/matthews/actionp.html Action potential propagation in myelinated and unmyelinated axons] at [[Blackwell Publishing]]
* [http://thevirtualheart.org/CAPindex.html Generation of AP in cardiac cells] and [http://thevirtualheart.org/java/neuron/apneuron.html generation of AP in neuron cells]
* [https://web.archive.org/web/20080414190744/http://bcs.whfreeman.com/thelifewire/content/chp44/4402001.html Resting membrane potential] from ''Life: The Science of Biology'', by WK Purves, D Sadava, GH Orians, and HC Heller, 8th edition, New York: WH Freeman, {{ISBN|978-0-7167-7671-0}}.
* [https://web.archive.org/web/20100808191814/http://www.nernstgoldman.physiology.arizona.edu/ Ionic motion and the Goldman voltage for arbitrary ionic concentrations] at The [[University of Arizona]]
* [https://web.archive.org/web/20081216233745/http://www.brainu.org/files/movies/action_potential_cartoon.swf A cartoon illustrating the action potential]
* [https://web.archive.org/web/20160611165335/http://1lec.com/action-potential/ Action potential propagation]
* [http://people.virginia.edu/~hvg2s/ Production of the action potential: voltage and current clamping simulations]{{dead link|date=October 2016 |bot=InternetArchiveBot |fix-attempted=yes }}
* [http://cese.sourceforge.net/ Open-source software to simulate neuronal and cardiac action potentials] at [[SourceForge.net]]
* [http://nba.uth.tmc.edu/neuroscience/s1/chapter01.html Introduction to the Action Potential], ''Neuroscience Online'' (electronic neuroscience textbook by UT Houston Medical School)
* [https://www.khanacademy.org/science/biology/human-biology/neuron-nervous-system/v/electrotonic-action%20potential Khan Academy: Electrotonic and action potential] {{Webarchive|url=https://web.archive.org/web/20140702113034/http://www.khanacademy.org/science/biology/human-biology/neuron-nervous-system/v/electrotonic-action%20potential |date=2 July 2014 }}

{{Authority control}}

{{DEFAULTSORT:Action Potential}}
[[Category:Capacitors]]
[[Category:Neural coding]]
[[Category:Electrophysiology]]
[[Category:Electrochemistry]]
[[Category:Computational neuroscience]]
[[Category:Cellular neuroscience]]
[[Category:Cellular processes]]
[[Category:Membrane biology]]
[[Category:Plant intelligence]]
[[Category:Action potentials]]