The ultrarapid delayed rectifier potassium current has important functional role in the repolarization reserve of canine and human ventricular muscle

Abstract The ultrarapid delayed rectifier potassium current (I Kur ) has long been considered an atrial‐specific current with no functional role in the ventricles, despite evidence of its expression in ventricular myocytes. In the present study we challenged this prevailing concept and investigated the potential role of I Kur in ventricular repolarization. Kv1.5 protein expression was determined by immunocytochemistry in canine and undiseased human cardiac tissue samples. Action potentials (APs) were recorded using conventional microelectrode techniques in canine and human cardiac preparations, and ion currents were measured using the whole‐cell patch‐clamp technique in isolated cardiomyocytes. In silico simulations were performed to investigate the role of the I Kur current using a human ventricular model (T‐World IKur ). Kv1.5 protein expression was detected in canine atrial, ventricular and Purkinje fibre cells, as well as in undiseased human left ventricular myocardium. In canine atrial preparations I Kur inhibition shifted the plateau phase of the AP into the positive voltage direction and consequently shortened AP duration. Application of 100 µM 4‐aminopyridine (4‐AP) revealed ionic currents of similar magnitude in ventricular myocytes and Purkinje fibres, which were attributed to I Kur . Inhibition of I Kur caused prolongation of the APs recorded from endocardial and midmyocardial preparations, as well as from Purkinje fibres. Under conditions of attenuated repolarization reserve I Kur inhibition induced augmented repolarization lengthening and frequent early afterdepolarizations (EADs). In silico modelling data regarding the I Kur inhibition‐evoked EAD formations are in good agreement with the experimental findings. I Kur is present and functionally active in ventricular myocardium and may represent a significant contributor to ventricular repolarization reserve. image Key points The ultrarapid delayed rectifier potassium current (I Kur ) has long been considered an atrial‐specific current with no functional role in the ventricles. In the present study, we challenged this prevailing concept and investigated the potential role of I Kur in ventricular repolarization. Cellular electrophysiology and molecular cardiological experiments were performed on cardiac preparations obtained from dog and undiseased human hearts. We present clear evidence that I Kur current is present in the ventricular myocardium at both molecular and functional levels. We also confirm that I Kur current plays a significant role in ventricular repolarization reserve. We concluded that I Kur is present and functionally active in ventricular myocardium and may represent a significant contributor to ventricular repolarization reserve.