[Transient outward potassium current and repolarization of cardiac cells]

Abstract

The transient 4-aminopyridine-sensitive outward potassium current, Ito, is one of the ionic membrane currents involved in the repolarization of cardiac action potentials. It is present in several species (rat, dog, human) but not in guinea pig ventricle. It induces both a marked lowering of the ventricular action potential plateau level and an early repolarization wave in the ventricular ECG complex of hypothermic rats. In dog ventricle where Ito is much shorter than the action potential plateau it can induce only a transient initial repolarization (notch). The distribution of Ito is heterogeneous across the dog left ventricular free wall, the current being of sizeable amplitude in epicardial and midmyocardial layers but absent in the endocardial layer. As a result, ventricular action potentials exhibit a notch only in epicardial and mid layers. Although the physiological role of Ito remains unclear, we suggest that it can participate in the control of calcium current intensity by influencing the level of the initial part of the plateau. In pathophysiological conditions, Ito may exert unfavourable effects, specially during simulated ischemia when the notch reaches the cellular repolarization threshold, thus inducing premature termination of the action potential, an obvious cause of drastic electrical heterogeneity and resulting severe arrhythmias. The current Ito is reduced in moderate cardiac hypertrophy and dilatation and almost entirely suppressed in severe hypertrophy. Ito is of larger amplitude in human atrial than in ventricular myocytes. The heterogeneous distribution of Ito described in the dog has also been found in human ventricles. Because Ito is markedly prolonged at low temperatures it is suggested that it can be responsible for the early repolarization wave (J wave) observed in the ECG of subjects submitted to hypothermia.