the Cardiac IKs Potassium Channel

The IKs potassium channel, critical to control of heart electrical activity, requires assembly of pore-forming alpha subunits (KCNQ1) and accessory beta (KCNE1) subunits. IKs is the slowly activating component of delayed rectifier K+ current in the heart and is a major contributor to the timing of repolarization of the cardiomyocyte membrane potential. Inherited mutations in either IKs channel subunit are associated with cardiac arrhythmia syndromes, including long QT syndrome (LQTS), short QT syndrome (SQTS) and familial atrial fibrillation (FAF). The biophysical properties of IKs channel current are dramatically altered when KCNE1 associates with the KCNQ1 channel. Functional tetrameric channels can be formed by KCNQ1 alone, but co-assembly with KCNE1 is required for the unique kinetics necessary to regulate human cardiac electrical activity as well as for the channel’s functional response to the sympathetic nervous system. Specifically, KCNE1 co-assembly results in a depolarizing shift in the voltage dependence of activation, an increase in the single channel conductance, and an increase in current density. IKs channel current is also characterized by slow activation and deactivation kinetics, with little or n