NervousPhysiological process

Action potential

Also known as: nerve impulse, spike, AP, saltatory conduction, refractory period

A brief (≈1–2 ms), all-or-none reversal of membrane potential, from ≈ −70 mV to ≈ +30 mV and back. Voltage-gated Na⁺ and K⁺ channels generate it, and it propagates without decrement along the axon.

Chemical Synapse Neuron & Action Potential

Overview

Resting potential≈ −70 mV

Threshold≈ −55 mV

Peak (overshoot)≈ +30 mV

After-hyperpolarisation≈ −80 to −90 mV

Duration (neuron)≈1–2 ms

Conduction velocity0.5–2 (C) to ≈120 m/s (Aα)

When graded synaptic potentials depolarise the axon initial segment to threshold (≈ −55 mV), enough voltage-gated Na⁺ channels open to start a positive-feedback loop, the Hodgkin cycle: depolarisation opens more Na⁺ channels, Na⁺ influx depolarises further, and so on. The membrane potential shoots toward E_Na and overshoots to ≈ +30 mV. Two processes then end the spike. Na⁺ channels inactivate: the h gate, an inactivation "ball and chain", closes within about a millisecond. Meanwhile slower voltage-gated (delayed-rectifier) K⁺ channels open, and K⁺ efflux repolarises the membrane. Because the K⁺ channels close slowly, the membrane briefly hyperpolarises toward E_K (≈ −80 to −90 mV), the after-hyperpolarisation, before returning to rest. Very few ions actually cross the membrane in a single action potential. The Na⁺/K⁺-ATPase restores the gradients over the long term but is not needed for individual spikes.

The action potential is all-or-none: once threshold is reached, amplitude does not depend on stimulus strength. Stimulus intensity is therefore coded by frequency of firing and by the number of fibres recruited. During the absolute refractory period, from threshold until repolarisation is well advanced, no second spike is possible, because Na⁺ channels are either open or inactivated. This limits maximum firing rate and makes propagation one-way. During the following relative refractory period, which coincides with the after-hyperpolarisation, a stronger-than-normal stimulus can trigger a spike, because some Na⁺ channels have recovered but K⁺ conductance is still elevated.

Propagation: local currents depolarise the adjacent membrane to threshold. In unmyelinated axons the spike regenerates continuously along the membrane (continuous conduction, 0.5–2 m/s). In myelinated axons it regenerates only at the nodes of Ranvier (saltatory conduction, up to ≈120 m/s). Conduction velocity increases with axon diameter (lower internal resistance), myelination and temperature.

Parts & subdivisions

1 · Resting state (≈ −70 mV)
Voltage-gated Na⁺ channels closed but ready (m gate closed, h gate open). K⁺ leak dominates.
2 · Depolarisation to threshold (≈ −55 mV)
Graded EPSPs summate at the axon hillock and initial segment, which has the highest density of Na⁺ channels. Na⁺ entry now outpaces K⁺ efflux.
3 · Rapid depolarisation / upstroke (to ≈ +30 mV)
Explosive opening of voltage-gated Na⁺ channels (positive feedback). Na⁺ rushes in, the membrane becomes inside-positive (overshoot), approaching but not reaching E_Na (+60 mV).
4 · Repolarisation
Na⁺ channels inactivate (h gate closes) and delayed-rectifier voltage-gated K⁺ channels open. K⁺ efflux returns the potential toward negative values.
5 · After-hyperpolarisation (≈ −80 to −90 mV)
K⁺ channels close slowly, so the potential undershoots toward E_K. This coincides with the relative refractory period.
6 · Return to rest
K⁺ channels close, leak channels restore the RMP, and Na⁺ channels recover from inactivation (h gate reopens on repolarisation).
Absolute refractory period
≈1 ms. No stimulus, however strong, can elicit another AP, because Na⁺ channels are open or inactivated. It limits the maximum frequency and enforces unidirectional propagation.
Relative refractory period
A few ms. A suprathreshold stimulus is required, because of residual K⁺ conductance and partial Na⁺-channel recovery.

Function

Long-distance, non-decremental signalling along axons.
Triggers neurotransmitter release at axon terminals.
Encodes stimulus intensity as firing frequency (rate coding).

Physiology: Hodgkin and Huxley (1952, squid giant axon; Nobel 1963) described the AP quantitatively using voltage clamp, as sequential Na⁺ and K⁺ conductance changes. Threshold is not fixed. It rises with slow depolarisation (accommodation, from progressive Na⁺ inactivation) and falls when extracellular Ca²⁺ is low, because divalent cations normally screen membrane surface charge and stabilise Na⁺ channels. Cardiac and some neuronal APs add Ca²⁺ currents, which produce plateaus or bursts.

Clinical significance

Na⁺-channel blockers

Tetrodotoxin (puffer fish) and saxitoxin (shellfish poisoning) block voltage-gated Na⁺ channels from outside, causing paraesthesia and paralysis. Local anaesthetics (lidocaine) enter in the un-ionised form and block from inside. Their block is use-dependent, favouring rapidly firing pain fibres, and small fibres are affected first. Anti-epileptic drugs such as phenytoin and carbamazepine stabilise the inactivated state.

Hypocalcaemia and neuronal hyperexcitability

Low extracellular Ca²⁺ lowers the AP threshold, causing spontaneous firing: perioral and digital paraesthesia, carpopedal spasm (Trousseau sign), facial twitch on tapping the facial nerve (Chvostek sign), tetany, laryngospasm and seizures.

Demyelination and conduction

In MS and GBS the current leaks at demyelinated internodes, so conduction slows or blocks. Heat shortens Na⁺-channel opening and can precipitate block (Uhthoff phenomenon). Channelopathies (Na⁺, K⁺, Ca²⁺) cause epilepsy, periodic paralysis, myotonia and familial hemiplegic migraine.

Mnemonics

Channel sequence

"Sodium in, potassium out": Na⁺ in for the upstroke, K⁺ out for the downstroke.

Test yourself

The rapid depolarising upstroke of a neuronal action potential is caused by:

Opening of voltage-gated K⁺ channels
Activity of the Na⁺/K⁺-ATPase
Opening of voltage-gated Na⁺ channels
Opening of ligand-gated Cl⁻ channels

Answer: Opening of voltage-gated Na⁺ channels

At threshold (≈ −55 mV), voltage-gated Na⁺ channels open. Na⁺ influx depolarises the membrane further, which opens more channels (positive feedback), and the potential overshoots to ≈ +30 mV. Repolarisation follows from Na⁺ channel inactivation and the opening of delayed-rectifier K⁺ channels.

What chiefly causes the absolute refractory period?

Inactivation of voltage-gated Na⁺ channels
Depletion of synaptic vesicles
Hyperpolarisation by the Na⁺/K⁺ pump
Closure of K⁺ leak channels

Answer: Inactivation of voltage-gated Na⁺ channels

Once the inactivation (h) gates close, Na⁺ channels cannot reopen until the membrane repolarises and they reset. During this time no stimulus, however strong, can fire a second action potential. This makes conduction one-way and limits the maximum firing frequency.