Figure 1.

The ventricular action potential as a paradigm for cardiac electrophysiological activity. In the resting state, the voltage of the cell intracellular space is negative to the external environment. This reflects its higher K⁺ but lower Na⁺ and Ca²⁺ concentrations and its lower membrane permeability to Na⁺ and Ca²⁺ in comparison to K⁺. K⁺ efflux from the cell is then controlled by the inward rectifier K⁺ channel (I_K1). When excitation threshold is reached, a large Na⁺ influx (I_Na) into the cell through Na⁺ channels produces phase 0 depolarization. This is followed by activation of fast and slow transient outward K⁺ currents (I_tof and I_tos, respectively) mediating a K⁺ efflux driving a rapid phase 1 repolarization. There is also an activation of a depolarizing inward Ca²⁺ current through L-type Ca²⁺ channels (I_Ca), which initiates excitation contraction coupling. The reduced membrane K⁺ permeability due to I_K1 rectification combined with I_Ca maintains the action potential phase 2 plateau phase. Phase 3 repolarization is driven by K⁺ efflux through the rapid and slow delayed rectifier K⁺ channels (I_Kr and I_Ks, respectively), as well as I_K1. At the end of phase 3, the Na⁺ and Ca²⁺ that have accumulated in the cells are removed by the Na⁺, K⁺ pump, and the Na⁺, Ca²⁺ exchanger (NCX). The atrial action potential shows greater contributions to recovery from the ultrarapid delayed rectifier outward currents (I_Kur) and acetylcholine-activated inward rectifying K⁺ channel (I_KACH). Adapted with permission from Huang.¹