TRANSIENT OUTWARD POTASSIUM CURRENT AND R EPOLARIZATION OF CARDIAC-CELLS

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 earl y repolarization wave in the ventricular ECG complex of hypothermic ra ts. In dog ventricle where Ito is much shorter than the action potenti al plateau it can induce only a transient initial repolarization (notc h). The distribution of Ito is heterogeneous across the dog left ventr icular free wall, the current being of sizeable amplitude in epicardia l and midmyocardial layers but absent in the endocardial layer. As a r esult, ventricular action potentials exhibit a notch only in epicardia l and mid layers. Although the physiological role of Ito remains uncle ar, we suggest that it can participate in the control of calcium curre nt intensity by influencing the level of the initial part of the plate au. In pathophysiological conditions, Ito may exert unfavourable effec ts, specially during simulated ischemia when the notch reaches the cel lular repolarization threshold thus inducing premature termination of the action potential an obvious cause of drastic electrical heterogene ity and resulting severe arrhythmias. The current Ito is reduced in mo derate cardiac hypertrophy and dilatation and almost entirely suppress ed in severe hypertrophy. Ito is of larger amplitude in human atrial t han in ventricular myocytes. The heterogeneous distribution of Ito des cribed 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.