This lesson is mapped to AQA 7402 Section 3.6.2 — resting potential and action potential (refer to the official AQA specification document for exact wording). Neurones transmit information as transient, regenerative electrical events called action potentials. The ionic basis of the action potential is one of the showpiece achievements of twentieth-century biology — the experimental dissection associated with Alan Hodgkin and Andrew Huxley in the squid giant axon (paraphrasing their voltage-clamp reconstruction of Na⁺ and K⁺ currents) demonstrated that the impulse is built from purely physical movements of ions across a permeable membrane, with no requirement for any "vital force". Their Nobel-recognised mathematical model still underpins modern neuroscience and pharmacology, including the design of every local anaesthetic and many anti-epileptic drugs.
At A-Level the conceptual move you must make is to stop thinking of the action potential as a "signal travelling down a wire" and start thinking of it as a regenerative wave of ion movement, in which each tiny patch of membrane is briefly persuaded by neighbouring depolarisation to throw open its Na⁺ channels, briefly invert its membrane potential, and then quickly re-impose order. The whole event takes only about 2–3 milliseconds; it carries information not by amplitude but by the frequency and pattern with which it fires.
Key Definition: An action potential is a rapid, temporary reversal of the electrical potential difference across the axon membrane, caused by the sequential opening and closing of voltage-gated ion channels in response to a threshold stimulus.
The Resting Potential
When a neurone is not transmitting an impulse, it is said to be at rest. The inside of the axon is negatively charged relative to the outside. This potential difference across the membrane is the resting potential, typically around −70 mV in mammalian neurones.
How the Resting Potential is Maintained
The resting potential is established and maintained by several interacting mechanisms:
The sodium-potassium pump (Na⁺/K⁺-ATPase):
An active-transport carrier protein in the axon membrane.
It pumps 3 Na⁺ ions out of the axon for every 2 K⁺ ions pumped in, using one molecule of ATP per cycle.
This creates a net movement of positive charge out of the cell, contributing a small (~10 mV) electrogenic component to the negative interior.
Crucially, the pump maintains the concentration gradients: high Na⁺ outside (~145 mM), high K⁺ inside (~140 mM).
Potassium leak channels:
The axon membrane contains potassium ion channels that are open at rest, allowing K⁺ to diffuse out of the axon down its concentration gradient.
This outward movement of positive K⁺ ions makes the inside of the axon more negative.
This is the dominant contributor to the resting potential — the membrane is approximately 25 times more permeable to K⁺ than to Na⁺ at rest.
Sodium channels are closed at rest:
Voltage-gated Na⁺ channels are predominantly closed when the membrane is at −70 mV, so very little Na⁺ enters despite its strong inward electrochemical gradient.
Large organic anions:
Negatively charged proteins, amino acids, phosphates, and nucleic acids inside the axon are too large or too polar to cross the membrane, contributing fixed negative charge inside.
The resting potential predicted by the Nernst equation for a perfectly K⁺-selective membrane would be approximately −90 mV; the measured −70 mV reflects a small residual Na⁺ permeability and the electrogenic Na⁺/K⁺ pump.
Exam Tip: The resting potential is mainly due to K⁺ leaking out through open potassium channels. The Na⁺/K⁺ pump is essential for maintaining the concentration gradients but contributes only a small direct electrogenic effect. A common A* discriminator is naming K⁺ permeability rather than the pump as the dominant proximate cause.
Generating an Action Potential
When a neurone is stimulated, the following sequence of events occurs at the trigger zone of the axon (the axon hillock) and is then propagated down the axon. Each phase corresponds to a particular state of the voltage-gated channels.
1. Stimulus and Depolarisation
A stimulus causes voltage-gated Na⁺ channels to open at the point of stimulation (or, more commonly, an arriving EPSP from a synapse depolarises the axon hillock).
Na⁺ ions flood into the axon down their electrochemical gradient (high concentration outside, attracted by negative charge inside).
This influx of positive charge causes the membrane potential to become less negative (depolarisation).
If the depolarisation reaches the threshold (approximately −55 mV), an action potential is triggered. Below threshold, the membrane simply returns to rest.
2. Rapid Depolarisation
Once threshold is reached, more voltage-gated Na⁺ channels open in a positive feedback loop: each opening Na⁺ channel further depolarises the membrane, which opens more Na⁺ channels, and so on.
Massive Na⁺ influx causes the membrane potential to rapidly rise, reaching approximately +30 mV — the inside becomes momentarily positively charged relative to the outside.
This phase is extremely rapid, taking less than 1 ms.
3. Repolarisation
At approximately +30 mV, the voltage-gated Na⁺ channels inactivate (a separate inactivation gate plugs the channel even though the activation gate remains open).
Voltage-gated K⁺ channels open. These respond to the same depolarisation but with a slight kinetic delay — Hodgkin and Huxley quantified this delay as the discriminator that allows the action potential to fire at all.
K⁺ ions rush out of the axon down their concentration gradient, carrying positive charge out of the cell.
The membrane potential falls back towards the resting potential.
4. Hyperpolarisation (Undershoot)
The voltage-gated K⁺ channels are slow to close, so K⁺ continues to leave the axon even after the resting potential is reached.
The membrane potential temporarily becomes more negative than −70 mV (e.g. −80 mV).
This phase is the hyperpolarisation or undershoot, and is associated with the relative refractory period.
5. Restoration of the Resting Potential
The voltage-gated K⁺ channels eventually close.
The Na⁺/K⁺ pump works to restore the original ion distribution (3 Na⁺ out, 2 K⁺ in per ATP). Although the number of ions moved per action potential is tiny relative to the existing gradients, sustained firing without the pump would eventually run the gradients down.
The resting potential of −70 mV is re-established.
graph LR
A["Resting<br/>-70 mV<br/>K+ leak dominates"] --> B["Threshold<br/>-55 mV<br/>positive feedback"]
B --> C["Depolarisation<br/>+30 mV<br/>Na+ rushes in"]
C --> D["Repolarisation<br/>Na+ channels inactivate<br/>K+ channels open"]
D --> E["Hyperpolarisation<br/>-80 mV<br/>K+ leak continues"]
E --> A
style A fill:#27ae60,color:#fff
style C fill:#e74c3c,color:#fff
style D fill:#3498db,color:#fff
SVG Visualisation — The Action Potential Trace
The classic trace of membrane potential against time looks roughly like this:
The whole event lasts about 2–3 ms. The shape of the trace and the labels (resting, threshold, depolarisation, repolarisation, hyperpolarisation) are exam-staple content.
Summary of Ion Movements During an Action Potential
Phase
Membrane Potential
Ion Channels
Ion Movement
Resting
−70 mV
Na⁺ channels closed, K⁺ leak channels open
K⁺ leaks out
Depolarisation
−70 mV → +30 mV
Voltage-gated Na⁺ channels open
Na⁺ rushes in
Repolarisation
+30 mV → −70 mV
Na⁺ channels inactivate, voltage-gated K⁺ channels open
K⁺ rushes out
Hyperpolarisation
−70 mV → −80 mV
K⁺ channels slow to close
K⁺ continues out
Restoration
−80 mV → −70 mV
Na⁺/K⁺ pump active
3 Na⁺ out, 2 K⁺ in per ATP
The Threshold and the All-or-Nothing Principle
Threshold
The minimum level of depolarisation required to trigger an action potential is the threshold (about −55 mV in mammalian axons).
Subthreshold stimuli cause local depolarisation but do not open enough voltage-gated Na⁺ channels to initiate the positive feedback loop. The membrane returns to the resting potential without generating an action potential. These local potentials can summate in space and time (see lesson 2 — synaptic transmission).
All-or-Nothing Principle
If the threshold is reached, an action potential of a fixed size (~+30 mV peak amplitude) is always produced, regardless of the strength of the stimulus.
If the threshold is not reached, no action potential is generated.
There is no such thing as a "large" or "small" action potential — every action potential in a given neurone has the same amplitude. This is a defining feature of the action potential and a frequent source of A* discriminators.
How Does the Nervous System Encode Stimulus Intensity?
If all action potentials are the same size, how does the brain distinguish between a gentle touch and a hard push?
Frequency coding: A stronger stimulus generates a higher frequency of action potentials (more action potentials per second), not a larger action potential. This is the temporal code.
Recruitment: A stronger stimulus may also stimulate more neurones, increasing the total number of impulses reaching the brain. This is the spatial code (or "population coding").
Receptor selectivity: Different receptor types (touch, pressure, temperature, pain) project to different cortical regions, so the identity of the input is encoded by labelled lines — which neurones fire, not how they fire.
The Refractory Period
After an action potential, the neurone enters a refractory period during which it is difficult or impossible to generate another action potential.
Absolute Refractory Period
Lasts approximately 1–2 ms.
During this time, the voltage-gated Na⁺ channels are inactivated — they have a separate inactivation gate that blocks the channel, even though the voltage-activation gate is open. They cannot be reopened until the membrane has repolarised and a few milliseconds have passed.
No stimulus, however strong, can generate another action potential during this period.
Significance:
Ensures each action potential is a discrete, separate event — a "spike", not a continuous wave.
Ensures the action potential travels in one direction only — the region of membrane behind the action potential is in the refractory period and cannot be re-stimulated, so the propagating wave cannot reverse.
Relative Refractory Period
Follows the absolute refractory period, lasting several milliseconds.
During this time, the membrane is hyperpolarised and some Na⁺ channels are returning to their resting state.
A stronger-than-normal stimulus can trigger an action potential, but it is more difficult and the resulting AP may be slightly delayed or smaller in initial slope.
Significance:
Limits the maximum frequency of action potentials to about 500–1,000 per second in mammalian motor neurones.
Helps to encode stimulus intensity through frequency modulation — stronger stimuli generate higher firing rates, up to the ceiling set by the refractory period.
Propagation of the Action Potential
The action potential at one point on the axon membrane causes local currents that depolarise the adjacent region of membrane:
Na⁺ ions that have entered at the site of the action potential diffuse along the inside of the axon (axoplasm) towards the next region.
This depolarises the adjacent region to threshold, opening voltage-gated Na⁺ channels there.
A new action potential is generated in the adjacent region — the wave regenerates.
The previous region is in its absolute refractory period, so the impulse can only travel forward (away from the cell body in a motor neurone).
In myelinated neurones, this process occurs only at nodes of Ranvier (saltatory conduction — see lesson 0), dramatically increasing the speed.
Factors Affecting the Speed of the Action Potential
Factor
Effect
Reason
Myelination
Greatly increases speed (up to ~50×)
Saltatory conduction; impulse regenerates only at nodes; capacitance is reduced
Axon diameter
Larger = faster
Less electrical resistance in the axoplasm (analogous to a thicker wire)
This content sits in AQA 7402 Section 3.6.2 — resting potential, action potential, refractory period, all-or-nothing principle (refer to the official AQA specification document for exact wording). It is examined directly on Paper 2 and synoptically on Paper 3.