The cardiac I Ks channel, complex indeed

Abstract

The cardiac IKs channel is a major repolarization current in the heart that responds rapidly and robustly to sympathetic nervous system stimulation to ensure adequate diastolic filling time in the face of accompanying accelerated heart rate. In cardiac myocytes, the IKs channel is a macromolecular complex composed of a pore-forming α (KCNQ1) subunit and modulatory β (KCNE1) subunit, as well as intercellular proteins critical for controlling the phosphorylation state of the complex (1). Although KCNQ1 alone assembles to form a voltage-gated potassium channel, the presence of KCNE1 is required to reproduce the kinetic properties of the native IKs channel, and KCNE1 coassembly is necessary to mediate the characteristic IKs response to sympathetic stimulation (2). The importance of the KCNE1 subunit is evidenced by its role in IKs channelopathies: mutation in either KCNQ1 or KCNE1 can underlie congenital long QT syndrome, and the presence of the β subunit is reported to be required for the gain-of-function phenotype in two KCNQ1 mutations implicated in congenital atrial fibrillation (3, 4). Among the questions surrounding the nature of the KCNQ1–KCNE1 association is that of the stoichiometry of the α and β subunits. Because of its homology with the remainder of the Kv channel superfamily, KCNQ1 (Kv7.1) is thought to form channels consisting of four α subunits (5). The number …