Subunit interaction determines IKs participation in cardiac repolarization and repolarization reserve.

Abstract

The role of IKs, the slow delayed rectifier K+ current, in cardiac ventricular repolarization has been a subject of debate. We develop a detailed Markov model of IKs and its alpha-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 beta-subunit) confers kinetic properties on IKs 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. Because of its ability to form an available reserve, IKs can function as a repolarization reserve when IKr, the rapid delayed rectifier, is reduced by disease or drug and can prevent excessive action potential prolongation and development of arrhythmogenic early afterdepolarizations.