Resting Potential and Action Potential

Spec Mapping — OCR H420 Module 5.1.3 — Neuronal communication, content statements covering the establishment of the resting potential, the events of an action potential (depolarisation, repolarisation, hyperpolarisation, and refractory period), the all-or-nothing principle, and the propagation of the action potential along a neurone (refer to the official OCR H420 specification document for exact wording). This is the highest-stakes domain-correctness lesson in the whole module — almost every A-Level Biology error in nerve physiology lives somewhere in the AP phase sequence.

The action potential is the single most important event in neuronal physiology. In roughly two milliseconds, a neurone flips its membrane voltage from −70 mV to +30 to +40 mV and back again, in a precisely choreographed dance of sodium and potassium ions. Understanding every phase of this cycle — and why it works the way it does — is essential for OCR A-Level Biology A.

The ionic basis of the action potential was elucidated by Alan Hodgkin and Andrew Huxley in a series of papers published in 1952, for which they shared the 1963 Nobel Prize in Physiology or Medicine (with John Eccles, who described synaptic potentials). Working on the giant axon of the squid (~500 μm diameter, large enough to thread a wire electrode inside), they developed the voltage-clamp technique to measure ionic currents at constant membrane voltage. By substituting Na⁺-free seawater they isolated the K⁺ current; by digital subtraction they isolated the Na⁺ current. Their analysis revealed two voltage-gated conductances with quantitatively different kinetics — fast-activating, fast-inactivating Na⁺ channels, and slow-activating, non-inactivating K⁺ channels — and showed that these two conductances alone, combined with the membrane capacitance and the resting permeability, were sufficient to generate the entire action-potential waveform (paraphrase). Earlier, Bernstein (1902) had proposed that the resting potential arose from membrane permeability to K⁺ alone, a hypothesis refined by David Goldman (1943) into the Goldman-Hodgkin-Katz equation, which generalised the Nernst potential to multiple permeant ions. The Hodgkin-Huxley equations remain the cornerstone of computational neuroscience — every contemporary model of brain activity, from single neurones to whole brains, ultimately rests on their 1952 framework (paraphrase).

Key Definitions:

• Resting potential — the steady voltage across the membrane of an unstimulated neurone, typically about −70 mV (inside negative relative to outside).
• Action potential — a rapid, transient reversal of membrane potential from −70 mV to approximately +40 mV, followed by repolarisation.
• Threshold — the potential (~−55 mV) at which voltage-gated Na⁺ channels open en masse, initiating an action potential.
• All-or-nothing — principle that action potentials either occur fully or not at all, irrespective of stimulus strength beyond threshold.
• Refractory period — the time after an action potential during which another cannot fire (absolute) or can only fire with a stronger stimulus (relative).

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The Resting Potential — How It Is Set Up

At rest, the inside of a neurone is about 70 mV more negative than the outside. This requires two things: (1) unequal distributions of ions across the membrane, and (2) differential membrane permeability.

The Sodium–Potassium Pump

Embedded in the membrane is a protein pump called the Na⁺/K⁺ ATPase. It uses ATP to export three Na⁺ ions for every two K⁺ ions it imports. This:

• Establishes a Na⁺ concentration gradient: Na⁺ is ~10× more concentrated outside.
• Establishes a K⁺ concentration gradient: K⁺ is ~30× more concentrated inside.
• Contributes a small direct negative charge to the inside (since three positive ions leave for every two that enter).

Differential Permeability

A second factor — equally important — is that the membrane at rest is roughly 100 times more permeable to K⁺ than to Na⁺. This is because:

• There are many K⁺ leak channels open at rest, allowing K⁺ to diffuse out down its gradient.
• There are very few open Na⁺ channels at rest; voltage-gated Na⁺ channels are closed until threshold is reached.

As K⁺ leaks out, positive charge leaves the cell faster than it enters, generating the negative interior. An equilibrium is reached when the negative interior is sufficient to electrostatically oppose further K⁺ loss. This is the resting potential.

Impermeant Anions

Inside the neurone are large, negatively charged proteins and organic phosphates that cannot cross the membrane. These contribute to the negative interior charge and help set up the electrical gradient.

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The Action Potential — Phase by Phase

When a stimulus depolarises the membrane to threshold (around −55 mV), a chain of events unfolds that OCR expects you to describe in detail.

1. Depolarisation

Once threshold is reached, voltage-gated Na⁺ channels open. Na⁺ rushes into the cell down both its concentration gradient and its electrical gradient. The inside of the cell rapidly becomes more positive, then more positive than the outside, reaching about +40 mV. This is an example of positive feedback: opening Na⁺ channels depolarises the membrane further, opening yet more Na⁺ channels, and so on.

2. Repolarisation

At the peak of the action potential, two things happen:

• Voltage-gated Na⁺ channels close (they inactivate — a second gate called the inactivation gate swings across the pore).
• Voltage-gated K⁺ channels, which open more slowly, have now opened. K⁺ flows out of the cell down its electrochemical gradient.

The combination of stopping Na⁺ entry and starting K⁺ exit rapidly restores the interior negative potential.

3. Hyperpolarisation

Voltage-gated K⁺ channels close slowly. During the delay between the cell reaching −70 mV and the channels fully closing, K⁺ continues to leave the cell, making the interior briefly even more negative than the resting potential — typically to about −80 mV. This dip is called hyperpolarisation (or the "undershoot").

4. Return to Rest

Once the voltage-gated K⁺ channels close and the Na⁺/K⁺ pump has had time to work, the membrane returns to −70 mV and the normal ion gradients are restored. The cell is ready to fire again.

flowchart TB
    A["Resting: -70 mV<br/>Voltage-gated channels closed"] -->|Stimulus reaches threshold| B["Depolarisation<br/>Na+ channels open<br/>Na+ rushes in"]
    B -->|Reaches +40 mV| C[Peak]
    C -->|Na+ channels inactivate<br/>K+ channels open| D["Repolarisation<br/>K+ flows out"]
    D -->|K+ channels slow to close| E[Hyperpolarisation: -80 mV]
    E -->|Na+/K+ pump restores gradients| A

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A Graph of the Action Potential

If you plotted membrane voltage against time, you would see a characteristic spike:

Time (ms)	Voltage (mV)	Event
0	−70	Resting potential
0.5	−55	Threshold reached
1.0	+30 to +40	Peak (depolarisation)
2.0	−70	Repolarisation
3.0	−80	Hyperpolarisation
5.0	−70	Back to rest

OCR frequently shows this graph and asks you to identify the phases and explain what ions are doing at each point. Make sure you can draw and label it from memory.

+30 mV 0 mV −55 mV (threshold) −70 mV (rest) −80 mV Membrane potential (mV)

Time (ms) 0 1 2 3 4

Resting Threshold Peak (+30 mV) Depolarisation (Na⁺ IN via VGSC) Repolarisation (K⁺ OUT via VGKC; VGSC inactivated) Hyperpolarisation (K⁺ overshoot) Return to rest

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The Nernst Equation — Quantifying Ion Driving Forces

For each permeant ion, there is an equilibrium potential at which the chemical driving force (concentration gradient) and the electrical driving force (voltage gradient) exactly balance, so net flow is zero. This is given by the Nernst equation:

$E_{ion} = \frac{RT}{zF}\ln\frac{[ion]_{out}}{[ion]_{in}}$Eion​=zFRT​ln[ion]in​[ion]out​​

where $E_{ion}$Eion​ is the equilibrium potential (in volts), $R$R is the universal gas constant (8.314 J K⁻¹ mol⁻¹), $T$T is absolute temperature in kelvin (~310 K for a mammal), $z$z is the ion charge (+1 for Na⁺ and K⁺, +2 for Ca²⁺), $F$F is the Faraday constant (96,485 C mol⁻¹), and the ratio is of extracellular to intracellular concentration of the ion.

For typical mammalian neurone concentrations:

• K⁺: [K⁺]_in ≈ 140 mM, [K⁺]_out ≈ 5 mM → $E_K \approx -90\text{ mV}$EK​≈−90 mV.
• Na⁺: [Na⁺]_in ≈ 15 mM, [Na⁺]_out ≈ 145 mM → $E_{Na} \approx +60\text{ mV}$ENa​≈+60 mV.
• Cl⁻: [Cl⁻]_in ≈ 10 mM, [Cl⁻]_out ≈ 110 mM → $E_{Cl} \approx -65\text{ mV}$ECl​≈−65 mV.

The resting potential (−70 mV) sits between $E_K$EK​ and $E_{Na}$ENa​, but much closer to $E_K$EK​ because resting K⁺ permeability is much greater than resting Na⁺ permeability. During the peak of the action potential, the membrane becomes briefly more permeable to Na⁺ than to K⁺, so the potential approaches $E_{Na}$ENa​ (+60 mV) but never quite reaches it because K⁺ permeability is also rising and Na⁺ channels are inactivating. The Nernst equation is the master equation behind every membrane potential calculation in physiology.

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The All-or-Nothing Principle

One of the most important properties of the action potential is that it is all-or-nothing. If the stimulus is below threshold, nothing happens. If it is at threshold or above, an action potential of the same size is produced. Stronger stimuli do not produce bigger action potentials — they produce action potentials at higher frequency.

Why? Because the positive feedback that opens Na⁺ channels is so powerful that, once it begins, it always runs to completion. The cell is not able to produce a "half" depolarisation.

This has a crucial consequence: information about stimulus strength is encoded in frequency, not amplitude.

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The Refractory Period

For a short time after an action potential, the membrane cannot easily fire another. This is the refractory period, and it has two phases:

• Absolute refractory period (~1 ms): voltage-gated Na⁺ channels are inactivated (not merely closed) and cannot reopen until the membrane has returned to near resting potential. During this time, no stimulus, however strong, can trigger another action potential.
• Relative refractory period (~3 ms): Na⁺ channels have reset, but K⁺ channels are still open, so the membrane is hyperpolarised. A stronger-than-usual stimulus can trigger an action potential here.

The refractory period matters for three reasons:

1. It imposes a maximum frequency of action potentials (about 500 Hz in neurones, 1000 Hz in some).
2. It ensures one-way propagation. After the action potential has passed one point, that region is refractory — so the depolarisation of the next stretch cannot back-propagate.
3. It separates action potentials in time, making the digital "pulse code" unambiguous.

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Propagation Along the Axon

Once an action potential is initiated at the axon hillock, it propagates along the axon. In an unmyelinated axon, each patch of membrane must depolarise neighbouring regions to threshold, opening new voltage-gated Na⁺ channels. In a myelinated axon, propagation is saltatory (see lesson 2), jumping between nodes of Ranvier.

OCR examiners like to ask why an action potential only travels in one direction. The answer is the refractory period: the region behind the advancing action potential is unexcitable, so the depolarisation can only move forwards.

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Summary Table: Ion Movements in the Action Potential