Control of the cardiac action potential: The role of repolarization dynamics

Although the action potential (AP) can be considered an “old acquaintance” by now, the complexity of the mutual interplay between membrane potential course and the underlying currents can still hold secrets, whose revelation may help in the interpretation of otherwise puzzling observations. The aim of this brief review is to analyze such an interplay from two viewpoints: how membrane current sets membrane potential course and how membrane potential course may, in turn, affect individual channel activity. The outcome of this analysis leads to the general conclusion that considering the “dynamic” nature of membrane potential is of major importance in explaining the physiological and pharmacological modulation of the AP. To illustrate this conclusion, specific issues are discussed in the review including the applicability of the term “membrane resistance” under dynamic conditions, and the role of membrane potential velocity in determining “reverse rate-dependency” of drug effects on AP duration and in exposing “non-equilibrium” phenomena in channel gating.