Non-Canonical Mechanism of the VSD-PD Coupling in KCNQ1/KCNE1 Channels

Abstract

Introduction: Mutations of KCNQ1 are linked to diseases, such as cardiac arrhythmia and deafness. In cardiomyocytes, KCNQ1 co-expression with KCNE1 slows channel opening drastically and shifts the voltage dependence of opening by >40 mV. However, the molecular mechanisms by which KCNE1 alters the KCNQ1 function is not completely understood. KCNQ1 channels contain both a voltage-sensing domain (VSD) and a pore domain (PD). KCNQ1/KCNE1 channels open mainly when the VSD is in the fully activated state, whereas KCNQ1 expressed alone opens even when the VSD is in an intermediate state.