Source: Brain-Mind Odyssey, UC Berkeley
Tags: action potential, depolarisation, repolarisation, threshold potential, voltage-gated sodium channels, voltage-gated potassium channels, refractory period, absolute refractory period, relative refractory period, positive feedback loop, all-or-none, Hodgkin and Huxley, squid giant axon, electrophysiology, intracellular recording, extracellular recording
An action potential is a rapid, all-or-none electrical signal generated when a neuron's membrane potential reaches threshold. Sodium rushes in through voltage-gated channels (depolarisation), then potassium flows out to reset the membrane (repolarisation). The refractory period that follows ensures signals travel in one direction and prevents the neuron from firing continuously. Hodgkin and Huxley's work on the squid giant axon first described these ionic mechanisms in detail.
Action potential
A rapid, transient reversal of the membrane potential that propagates along the neuron's axon. It is the fundamental unit of neuronal signalling over distance.
Threshold
The membrane voltage (typically around -55 mV) at which a neuron is committed to firing an action potential. Below threshold, the signal dies out. At or above it, the positive feedback loop takes over.
Depolarisation
A shift in membrane potential toward less negative (or positive) values. During an action potential, this is driven by Na+ influx through voltage-gated sodium channels.
Repolarisation
The return of the membrane potential toward its resting value, driven by K+ efflux through voltage-gated potassium channels.
Hyperpolarisation (undershoot)
A brief period after repolarisation where the membrane potential dips below the normal resting level, because voltage-gated K+ channels are slow to close.
Voltage-gated sodium channel
A membrane protein that opens in response to depolarisation, allowing Na+ to flood into the cell. It also has an inactivation gate that closes shortly after opening, which is critical for repolarisation and the refractory period.
Voltage-gated potassium channel
A membrane protein that opens in response to depolarisation but with a slight delay compared to sodium channels. Allows K+ to exit the cell, driving repolarisation.
Refractory period
The interval after an action potential during which the neuron cannot (absolute) or is less likely to (relative) fire again. Caused by sodium channel inactivation and sustained potassium conductance.
Positive feedback loop
In the context of the action potential: depolarisation opens Na+ channels, Na+ influx causes further depolarisation, which opens more Na+ channels. This self-reinforcing cycle drives the rapid upstroke.
All-or-none principle
An action potential either fires fully or does not fire at all. There is no "partial" action potential. The amplitude is independent of stimulus strength.
Electrophysiology
The branch of physiology that studies the electrical properties of cells and tissues. In neurobiology, it refers to techniques for recording neuronal voltage and current.
A stimulus (from a synapse or sensory input) depolarises the neuron's membrane toward threshold
Once threshold is reached, voltage-gated Na+ channels open rapidly
Na+ rushes into the cell down its electrochemical gradient
The influx of positive charge depolarises the membrane further, opening still more Na+ channels
This is the positive feedback loop: depolarisation → channel opening → more depolarisation
The membrane potential shoots upward toward the sodium equilibrium potential (around +50 mV)
This is the upstroke (rising phase) of the action potential
The process is all-or-none: once threshold is crossed, the full action potential occurs regardless of stimulus strength
Voltage-gated K+ channels open in response to depolarisation, but with a slight delay relative to the Na+ channels
K+ flows out of the cell, carrying positive charge out and driving the membrane potential back down
Simultaneously, Na+ channels enter an inactivated state (distinct from simply being closed)
Inactivated channels cannot reopen until the membrane repolarises, regardless of voltage
The combination of K+ efflux and Na+ channel inactivation produces repolarisation
Because K+ channels close slowly, the membrane potential briefly overshoots the resting level (hyperpolarisation, or undershoot)
The refractory period has two phases:
Absolute refractory period: Na+ channels are inactivated, no stimulus of any strength can trigger another action potential
Relative refractory period: some Na+ channels have recovered, but a stronger-than-normal stimulus is needed to reach threshold (because of lingering K+ conductance and hyperpolarisation)
The refractory period ensures the action potential propagates in one direction along the axon and prevents the neuron from firing continuously
Ion channels are both selective (only certain ions pass) and gated (only open under specific conditions)
Gating can be voltage-dependent (responds to membrane potential changes) or ligand-dependent (responds to neurotransmitter binding)
Voltage-gated channels do not consume ATP directly
They rely on the ion gradients already established by the sodium-potassium pump
The pump does the energetic work; the channels allow that stored energy to be released as electrical signals
Selective permeability and gating together make the action potential possible
Intracellular recording: an electrode is inserted inside the cell to measure the exact membrane potential over time
Provides high-fidelity traces of action potentials and synaptic events
Technically difficult, especially in small neurons
Extracellular recording: electrodes placed outside the cell detect electrical disturbances from nearby neuronal activity
Less resolution than intracellular methods
Easier to perform and can record from many neurons at once
Worked on the giant axon of the squid (chosen for its large diameter, making electrode insertion feasible)
Produced the first detailed recordings of action potentials
Identified the separate ionic currents (Na+ and K+) underlying each phase
Developed a mathematical model describing how voltage-gated conductances produce the action potential
Awarded the Nobel Prize in Physiology or Medicine (1963)
Their framework remains the foundation of our understanding of neuronal excitability
Action potential phases (typical trace):
Resting state (~-70 mV)
Depolarisation to threshold (~-55 mV)
Rapid upstroke (Na+ influx) toward ~+40 mV
Repolarisation (K+ efflux) back toward resting level
Hyperpolarisation (undershoot) below resting, then gradual return
A sketch of the action potential waveform with these phases labelled is worth memorising for exams.
⚠️ The distinction between Na+ channel "closed" and "inactivated" is heavily tested. A closed channel can open if threshold is reached. An inactivated channel cannot open at all until the membrane repolarises and the inactivation gate resets. This is the mechanistic basis of the absolute refractory period.
⚠️ Know the timing: Na+ channels open first and fast, K+ channels open with a delay. This delay is what allows the upstroke to happen before repolarisation begins.
⚠️ Voltage-gated channels are passive (no ATP consumed). The sodium-potassium pump is active (consumes ATP). Exams like to test whether you know which one uses energy directly.
⚠️ The refractory period has two distinct phases (absolute and relative) with different mechanisms. Be precise about which channels and states are involved in each.
⚠️ Hodgkin and Huxley used the squid giant axon. This is a classic exam fact, including the reason (large diameter for easier recording).
Q: What is the positive feedback loop in action potential generation?
A: Depolarisation opens voltage-gated Na+ channels, Na+ influx causes further depolarisation, which opens more Na+ channels. This self-amplifying cycle drives the rapid upstroke of the action potential.
Q: Why can a neuron not fire a second action potential during the absolute refractory period?
A: Because the voltage-gated Na+ channels are in an inactivated state. They cannot reopen regardless of stimulus strength until the membrane repolarises and the inactivation gates reset.
Q: What is the difference between the absolute and relative refractory periods?
A: During the absolute refractory period, Na+ channels are inactivated and no action potential can be generated at any stimulus intensity. During the relative refractory period, some Na+ channels have recovered, but the lingering K+ conductance and hyperpolarisation mean a stronger-than-normal stimulus is needed to reach threshold.
Q: Do voltage-gated ion channels consume ATP?
A: No. They rely on the ion gradients established by the sodium-potassium pump. The channels themselves are passive, opening and closing in response to voltage changes without direct energy expenditure.
Q: Why did Hodgkin and Huxley use the squid giant axon for their experiments?
A: Its unusually large diameter made it possible to insert electrodes and record intracellular membrane potentials, which was not technically feasible in smaller neurons at the time.
Q: What causes the brief hyperpolarisation (undershoot) after an action potential?
A: Voltage-gated K+ channels are slow to close. K+ continues to flow out of the cell even after the membrane has returned to resting potential, briefly driving the voltage below the resting level.
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