The Action Potential, Phase by Phase (MCAT)

A neuron at rest sits near −70 mV inside relative to outside. Two things produce it, and questions often turn on distinguishing them.

The dominant cause is selective permeability. At rest the membrane is far more permeable to potassium than to sodium, because potassium leak channels are open. Potassium therefore flows down its concentration gradient out of the cell, leaving behind unbalanced negative charge. The resting potential sits near, but not exactly at, the potassium equilibrium potential — the small offset is due to slight sodium permeability.

The secondary cause is the sodium–potassium ATPase, which pumps three sodium ions out for every two potassium ions in. It is electrogenic and contributes a few millivolts directly, but its main role is maintaining the concentration gradients that make the leak-driven potential possible. Its contribution to the voltage is small; its contribution to sustaining the system is essential.

The distinction is tested directly. Blocking the pump does not immediately abolish the resting potential — gradients run down over many cycles. Blocking potassium leak channels changes it immediately.

The two-gate structure of the voltage-gated sodium channel is the detail that explains the most. It has an activation gate that is closed at rest and opens quickly on depolarization, and a separate inactivation gate that is open at rest and closes slowly after depolarization. Because the gates operate on different timescales, the channel opens, then shuts itself, without waiting for the voltage to fall.

Sodium-channel inactivation is what terminates depolarization, and delayed potassium-channel opening is what drives repolarization. Both are needed; questions often ask you to attribute a specific phase to one of them.

Below threshold, a stimulus produces a graded local depolarization that decays with distance and does not propagate. At threshold, sodium entry becomes self-reinforcing: entering sodium depolarizes the membrane, which opens more sodium channels, which admits more sodium. That positive feedback runs to completion regardless of how far past threshold the stimulus went.

So a stimulus is either sufficient or it is not, and the resulting spike has the same amplitude either way. Stimulus intensity is not encoded in the size of an action potential — it is encoded in firing frequency and in how many neurons are recruited. This is a frequent answer choice trap: a stronger stimulus does not produce a taller spike.

During the absolute refractory period no stimulus of any strength can trigger another action potential, because the sodium channel inactivation gates are closed and cannot reopen until the membrane repolarizes. This is a property of the channel, not a matter of stimulus strength.

During the relative refractory period a stronger-than-usual stimulus can trigger a spike. Sodium channels have largely reset, but the membrane is hyperpolarized and potassium channels remain open, so more depolarization is required to reach threshold.

Two consequences are commonly tested. Refractory periods set the maximum firing frequency, which caps how much stimulus intensity a single neuron can encode. And they enforce unidirectional propagation: the stretch of membrane just behind the advancing impulse is refractory, so the signal cannot double back.

Two factors determine how fast an impulse travels, and both work by the same underlying mechanism — reducing the loss of current across the membrane so that depolarization spreads further before it must be regenerated.

Myelin is an insulating sheath produced by oligodendrocytes in the central nervous system and Schwann cells in the peripheral nervous system. It increases membrane resistance, so local current spreads down the axon rather than leaking out. Voltage-gated sodium channels are concentrated at the nodes of Ranvier, the gaps between myelin segments, and the action potential is regenerated only there. This is saltatory conduction, and it is faster and more metabolically efficient because far less sodium must be pumped back out.

Larger axon diameter increases speed by decreasing internal resistance to current flow, in the same way a wider pipe offers less resistance. Invertebrates lacking myelin achieve fast conduction through very large axons; vertebrates achieve it more economically with myelin.

Demyelinating conditions such as multiple sclerosis illustrate the mechanism. Losing myelin allows current to leak across the internodal membrane, so depolarization may fail to reach the next node and conduction slows or fails — which is why passages on demyelination expect you to predict slowed or blocked conduction rather than altered spike amplitude.

Attributing repolarization to the sodium–potassium pump. The pump is far too slow to shape a millisecond-scale event. Repolarization is voltage-gated potassium efflux; the pump restores gradients over a longer timescale.

Thinking a stronger stimulus produces a bigger action potential. Amplitude is fixed once threshold is crossed. Intensity is encoded by frequency and recruitment.

Confusing hyperpolarization with the resting state. The undershoot below −70 mV occurs because potassium channels close slowly and stay open slightly too long — it is potassium overshoot, not a return to baseline.

Assuming ion movements meaningfully change bulk concentrations. Very few ions cross per spike relative to the total present; the voltage changes without any appreciable change in intracellular sodium or potassium concentration. This is why a neuron can fire repeatedly before gradients need restoring.

Mixing up which glial cell myelinates where. Oligodendrocytes myelinate multiple axons in the central nervous system; Schwann cells myelinate a single segment of one axon in the peripheral nervous system.