In a slice preparation, investigators patch-clamped a cortical pyramidal neuron and applied a selective blocker of voltage-gated K channels at the axon initial segment (AIS) while keeping all synaptic inputs constant. The concept tested is ion permeability during the action potential. Which change is most consistent with this manipulation and would be expected to increase action potential firing during a sustained depolarizing current step?
A pilot dataset showed spike half-width increased from 1.1 ms to 1.8 ms after drug application, with resting membrane potential unchanged.
- Decreased refractory period due to faster repolarization, allowing earlier Na channel recovery
- Increased spike frequency because slower repolarization reduces Na channel inactivation during each spike
- Decreased spike frequency because delayed repolarization prolongs Na channel inactivation and lengthens the effective refractory period (correct answer)
- No change in spike frequency because K conductance affects only synaptic potentials, not action potentials
Explanation: This question assesses understanding of action potentials and synaptic transmission, focusing on ion permeability during the action potential. Action potentials involve depolarization through Na+ influx followed by repolarization via K+ efflux, with refractory periods influenced by channel recovery times. In this scenario, blocking voltage-gated K+ channels at the AIS delays repolarization, broadening the action potential as shown by increased spike half-width. Choice C is correct because it aligns with the principle that delayed repolarization prolongs Na+ channel inactivation, reducing spike frequency during sustained depolarization. Choice B fails as it misapplies the effect of slower repolarization by suggesting reduced inactivation, when it actually extends the inactivated state. To avoid similar mistakes, always consider how alterations in repolarizing currents affect the duration of refractory periods and overall firing rates.