Action Potential: Ionic Mechanisms

Abstract

Abstract The generation and propagation of the action potential require sodium influx via voltage‐dependent sodium channels that drive the upstroke of the action potential. This positive feedback cycle is terminated by sodium channel inactivation that shuts down the channel at depolarised membrane potentials. The reduced sodium influx along with increased potassium efflux permits rapid action potential repolarisation. 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 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 depolarises 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 depolarised. The reduction of sodium influx resulting from inactivation combined with potassium efflux from the cell via voltage‐dependent and/or voltage‐independent potassium channels drive the repolarisation phase of the action potential. The voltage‐dependent potassium channels often remain active following the action potential (slow to close) to generate an afterhyperpolarization (AHP). The AHP can speed sodium channel recovery from inactivation, which is faster at more hyperpolarised 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 vs. 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.