Role of potassium channels in cycle length dependent regulation of action potential duration in mammalian cardiac Purkinje and ventricular muscle fibres.

Abstract

This review examines the putative role played by three repolarising potassium currents, namely the transient outward current (ito), the inward rectifying current (iK1), and the late outward rectifying current (iK), in the regulation of action potential duration in cardiac Purkinje and ventricular muscle fibres under normal physiological conditions. The role of other potassium currents, including the ATP activated current (iK,ATP) under these conditions is uncertain. Personal experiences and work of others are reviewed to summarise: (1) regulation of normal cycle length dependent action potential duration: (2) the characteristics of ito, iK1, and iK pertinent to repolarisation; and (3) the effects of potassium channel blockers and activators on cycle length dependent action potential duration. The presence of ito creates a notch after depolarisation and limits action potential duration at long cycles. Block of iK1 prolongs action potential duration predominantly by slowing phase 3 of the action potential. Block of iK prolongs the duration predominantly by lengthening phase 2 of the action potential, and the lengthening becomes more pronounced at longer cycles. Activation of iK,ATP shortens the duration, and the shortening becomes more pronounced at longer cycles. Each of the three major repolarising potassium currents appears to play a different role in modulating the action potential duration. Ito creates a notch which resets the early course of plateau, and also limits the duration at long cycles. IK1 contributes to maintenance of plateau and controls repolarisation course during phase 3 of the action potential. IK plays major role in controlling action potential duration within a wide range of cycle lengths in Purkinje fibres, and when present, also in ventricular muscle fibres.