MinK: a double-hearted partner in cardiac repolarization

Tight control of the cardiac repolarization process is essential to ensure adequate action potential duration. When cardiac repolarization is disturbed—e.g. by ion-channel mutations, drugs, or disease-related defects—rhythm disturbances may ensue. Thus, a delay in repolarization, apparent in the ECG as a long QT interval, may induce early afterdepolarizations that give rise to Torsades de Pointes and can lead to life-threatening arrhythmias.1 On the other hand, a premature repolarization, resulting in a short QT interval, has also been associated with a high rate of sudden cardiac death.2 Two important players in controlling repolarization and duration of the cardiac action potential are the delayed rectifying outward potassium currents, the fast activating IKr and the slowly activating IKs. In most species, repolarization seems to be dominated by activation of IKr, since IKs normally activates slowly and with a delay such that its magnitude is minute at the end of the action potential. Hence, IKs is supposed to act as a safety net for repolarization,3 coming into play when repolarizing currents like IKr fail. IKs, therefore, acts as a repolarization reserve.4