Subunit Interaction Determines I Ks Participation in Cardiac Repolarization and Repolarization Reserve

Abstract

Background— The role of I Ks , the slow delayed rectifier K + current, in cardiac ventricular repolarization has been a subject of debate. Methods and Results— We develop a detailed Markov model of I Ks and its α-subunit KCNQ1 and examine their kinetic properties during the cardiac ventricular action potential at different rates. We observe that interaction between KCNQ1 and KCNE1 (the β-subunit) confers kinetic properties on I Ks that make it suitable for participation in action potential repolarization and its adaptation to rate changes; in particular, the channel develops an available reserve of closed states near the open state that can open rapidly on demand. Conclusions— Because of its ability to form an available reserve, I Ks can function as a repolarization reserve when I Kr , the rapid delayed rectifier, is reduced by disease or drug and can prevent excessive action potential prolongation and development of arrhythmogenic early afterdepolarizations.