Questions: Action Potential Repolarization and Undershoot

Question 1

At the peak of an action potential (+30 mV), the membrane begins to repolarize back toward resting potential. What is the primary mechanism driving this repolarization?

• A. Voltage-gated Na+ channels begin closing in response to the positive membrane potential
• B. The Na+/K+ ATPase pump immediately activates and restores the ion gradients
• C. Voltage-gated Na+ channels have inactivated while voltage-gated K+ channels have now reached peak conductance, producing outward K+ current
• D. Ca2+ channels open and compete with Na+ channels, diluting the inward current

Answer: (C)

Repolarization is driven by a timing mismatch between two channel populations. Voltage-gated Na+ channels activate fast but also inactivate fast — within ~1 ms, an inactivation gate blocks the pore even as the activation gate remains open. This stops Na+ influx. Meanwhile, voltage-gated K+ channels, which activate much more slowly, are now reaching peak open probability. The resulting outward K+ current drives the membrane back toward the K+ equilibrium potential (~−80 mV). The Na+/K+ ATPase (option B) is far too slow to drive repolarization — it restores ion gradients over much longer timescales.

Question 2

Why does the action potential 'undershoot' — transiently hyperpolarizing below resting membrane potential after repolarization?

• A. The Na+/K+ ATPase pumps extra K+ in during recovery, lowering the membrane potential
• B. Voltage-gated Na+ channels reopen briefly after inactivation, generating an inward current that overshoots
• C. K+ channels reach peak conductance after the membrane has passed through resting potential, so K+ continues flowing outward before channels close
• D. Cl- channels open during repolarization and pull the membrane below resting potential

Answer: (C)

The undershoot occurs because K+ channel closing is delayed. These channels reach peak open probability as the membrane is falling from +30 mV, and they are still maximally open as the membrane passes through resting potential (~−65 mV). Because the K+ equilibrium potential (~−80 mV) is below resting, K+ continues flowing outward, pulling the membrane below resting potential. Only as K+ channels gradually close does the membrane drift back to its resting value — purely a consequence of slow K+ channel kinetics, not an active pumping process.

Question 3

Voltage-gated K+ channels reach their maximum open probability later in the action potential than voltage-gated Na+ channels — after Na+ channels have already inactivated.

• T. True
• F. False

Answer: True

This timing difference is the entire mechanistic basis of repolarization. Both channel types respond to the same membrane depolarization, but Na+ channels activate within a fraction of a millisecond while K+ channels activate much more slowly. By the time K+ conductance peaks, Na+ channels have already inactivated. The resulting brief window of dominant K+ conductance — unopposed by inward Na+ current — drives the membrane back toward the K+ equilibrium potential and produces the undershoot.

Question 4

Inactivation of voltage-gated Na+ channels during an action potential is the same process as channel closing — both return the channel to a resting state ready to reopen on the next stimulus.

• T. True
• F. False

Answer: False

Inactivation and closing (deactivation) are distinct conformational states. A closed channel can reopen when the membrane depolarizes again. An inactivated channel cannot reopen until the membrane repolarizes — a cytoplasmic 'ball' has physically blocked the pore, and this state requires hyperpolarization to reverse. This distinction is crucial: during the absolute refractory period, Na+ channels are inactivated, not just closed, which is why no stimulus (however strong) can trigger another action potential until inactivation is reversed.

Question 5

Explain why the afterhyperpolarization (undershoot) makes it harder to fire another action potential immediately after the first. What is the functional significance of this for the neuron?

Model answer: During the undershoot, the membrane potential is below resting potential — farther from the threshold for firing. A stronger-than-normal depolarizing stimulus is therefore required to reach threshold, defining the relative refractory period. This limits maximum firing rate. Combined with the absolute refractory period (when Na+ channels are inactivated), the undershoot also ensures that action potentials propagate in only one direction — the region behind a propagating spike is refractory and cannot be re-excited.

The refractory period is not a bug but a feature. It encodes temporal separation between signals (minimum inter-spike interval), enforces unidirectional propagation along axons, and allows partial restoration of ion gradients before the next spike. Without it, a single stimulus could set off a reverberating wave that bounced back and forth indefinitely. The undershoot's contribution to the relative refractory period is one of the elegant self-limiting mechanisms of neural signaling.