Action Potential: Ionic Mechanisms

Abstract

Abstract The generation and propagation of the action potential requires sodium influx via voltage‐dependent sodium channels that drives the upstroke of the action potential. This positive feedback cycle is terminated by sodium channel inactivation that shuts down the channel at depolarized membrane potentials. The reduced sodium influx along with increased potassium efflux permits rapid action potential repolarization. The enhanced potassium efflux is mediated by the activity of both voltage‐dependent and voltage‐independent potassium channels. The recovery of sodium channels from inactivation and the slow closing of potassium channels following the action potential determine the refractory period, which is a period of increased action potential threshold. Thus, the kinetics of sodium and potassium channel gating determine not only the action potential shape and duration, but also the threshold for action potential generation. Key concepts: Sodium influx via voltage‐dependent sodium channels depolarizes the membrane to activate more sodium channels in a positive feedback mechanism that generates the ballistic rising phase of the action potential. This positive feedback cycle is terminated by a separate gating process called inactivation, which shuts down sodium flux even though the membrane is still depolarized. The reduction of sodium influx resulting from inactivation combined with potassium efflux from the cell via both voltage‐dependent and voltage‐independent potassium channels drive the repolarization phase of the action potential. The voltage‐dependent potassium channels often remain active following the action potential (slow to close) to generate an after‐hyperpolarizing potential (AHP). The AHP can speed sodium channel recovery from inactivation, which is faster at more hyperpolarized voltages, so that the channels are more rapidly reset to participate in generating the next action potential. Action potential threshold is determined by the relative activity of sodium versus potassium channels with an action potential being generated if the sodium influx is larger than the potassium efflux. Insulating the axon with myelin increases the speed of action potential propagation by limiting action potential generation to small unmyelinated gaps called nodes of Ranvier. High‐density clustering of sodium channels at the nodes of Ranvier ensures sufficient current is generated to exceed threshold at the next node so that the action potential is faithfully propagated along the axon.