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The action potential in mammalian central neurons

Key Points

  • Neuronal cell bodies in the mammalian CNS typically have more than a dozen distinct voltage-dependent conductances. The greater number of conductances compared to the squid axon is associated with much more complex firing patterns than can be produced by the squid axon.

  • Action potential shapes and firing patterns differ widely among different types of neurons.

  • One recognizable phenotype is that of fast-spiking neurons, which are capable of firing steadily at high frequencies and have narrow action potentials. This phenotype is typical of many interneurons and is associated with the expression of Kv3 family potassium channels.

  • Some neurons with fast-spiking behaviour express resurgent sodium current, a component of tetrodotoxin-sensitive current that flows after the spike and promotes high-frequency firing.

  • Most neurons have large calcium currents carried by multiple types of calcium channels. The calcium current is largest during the falling phase of the action potential but is often outweighed by calcium-activated potassium current, activated by extremely rapid coupling to calcium entry.

  • Potassium channels commonly playing a major part in the repolarization of action potentials include Kv3 channels, IA (Kv4) channels, ID (Kv1) channels and large conductance calcium-activated potassium (BK) channels.

  • Inactivation of potassium currents can produce frequency-dependent broadening of the action potential, which can produce synaptic facilitation. Potassium channels whose inactivation can lead to frequency-dependent spike broadening include BK channels and inactivating Kv1 family channels located in presynaptic terminals.

  • Following the spike, many neurons have afterpotentials, including multiple types of afterhyperpolarizations with time courses lasting up to several seconds. Pyramidal neurons often have a prominent afterdepolarization which, if large enough, can lead to all-or-none bursting.

  • Currents active at subthreshold voltages can greatly influence firing patterns and frequency. These include IA and ID potassium currents, steady-state “persistent” sodium current, T-type calcium current, and the hyperpolarization-activated cation current called Ih.

  • The system of ionic currents that controls action potential shape and firing patterns in central neurons, although complex, has remarkable advantages for pursuing general problems in systems biology (such as robustness and redundancy): it has highly quantifiable elements, which are well-suited to mathematical modelling.


The action potential of the squid giant axon is formed by just two voltage-dependent conductances in the cell membrane, yet mammalian central neurons typically express more than a dozen different types of voltage-dependent ion channels. This rich repertoire of channels allows neurons to encode information by generating action potentials with a wide range of shapes, frequencies and patterns. Recent work offers an increasingly detailed understanding of how the expression of particular channel types underlies the remarkably diverse firing behaviour of various types of neurons.

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Figure 1: Diversity of action potentials in central neurons.
Figure 2: Phase-plane plots and action potential clamp.
Figure 3: Sodium, calcium, and calcium-activated potassium currents during action potentials.
Figure 4: Role of Kv3 potassium currents in fast-spiking neurons.
Figure 5: Frequency-dependent spike broadening from inactivation of potassium current.
Figure 6: Afterhyperpolarizations, afterdepolarizations, and all-or-none burst firing.


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I am grateful to M. Puopolo, M. Martina, B. Carter and A. Swensen for permission to use their unpublished data, and to them, Z. Khaliq and A. Jackson for much helpful discussion. Supported by the National Institute of Neurological Diseases and Stroke (NS36855).

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Heterologous expression

Expression of protein molecules by the injection of complementary RNA into the cytoplasm (or complementary DNA into the nucleus) of host cells that do not normally express the proteins, such as Xenopus oocytes or mammalian cell lines.


Another term for an action potential (especially the portion with the most rapidly changing voltage).

Projection neurons

Neurons with relatively long axons that project out of a local circuit (distinct from interneurons).


The firing of a rapid series of several action potentials with very short (less than 5 ms) interspike intervals.


Slowing or cessation of firing during a maintained stimulus.

Initial segment

The slender initial region of an axon where it originates from an axon hillock of the cell body (or sometimes from a major dendrite), characterized by the fasciculation of microtubules.

Node of Ranvier

Interruption of the myelin sheath in a myelinated nerve fibre.

Outside-out patch

A variant of the patch-clamp technique in which a patch of plasma membrane covers the tip of the electrode, with the outside of the membrane exposed to the bathing solution.


Conformational change of a channel molecule from a closed (non-conducting) to an open (conducting) state (for voltage-dependent channels, this is usually by depolarization of the membrane).

Subthreshold voltages

Voltages negative to the threshold voltage (Box 1) for action potential firing (which is typically in the range of −55 mV to −40 mV in mammalian central neurons).


(TTX). Alkaloid toxin derived from Fugu puffer fish that is a potent and highly selective blocker of voltage-dependent sodium channels.


Conformational change of a channel molecule to a closed state that differs from the closed 'resting' state in that the channel cannot be opened (for example, by further depolarization).


Potassium channel blocker that inhibits some potassium channels (including Kv3 family channels and a subset of Kv1 family subunits) with a high relative potency and others (such as Kv4 channels) more weakly, or not all.

Tetraethylammonium ion

(TEA). When applied externally, this blocks some types of voltage-activated potassium channels (notably BK and Kv3 family channels) and not others.

Delayed-rectifier current

Depolarization-activated potassium current similar to that of the squid axon, with relatively slow activation and minimal (or very slow) inactivation.


Measure of steepness of voltage-dependent activation, associated with a description by the Boltzmann function; e-fold increase is a 2.72-fold increase.


Voltage at which activation is half-maximal.

Rebound bursting

Firing of a burst of action potentials when a hyperpolarizing influence (such as inhibitory postsynaptic potential) is terminated.

Electrotonic length constant

Measure of the distance over which a voltage change imposed at one point in a cable-like structure decays to 1/e (37%).

Pacemaking neurons

Neurons that fire spontaneous action potentials in a regular, rhythmic manner.

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Bean, B. The action potential in mammalian central neurons. Nat Rev Neurosci 8, 451–465 (2007).

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