Structural basis for KV7.1–KCNEx interactions in the IKs channel complex

The cardiac IKs current is involved in action potential repolarization, where its primary function is to limit action potential prolongation during sympathetic stimulation. The IKs channel is mainly composed of KV7.1 ion channels associated with KCNE1 auxiliary subunits. The availability of KCNE1 solution structure by nuclear magnetic resonance spectroscopy in conjunction with biochemical assays addressing KV7.1–KCNE1 residue interactions has provided new insights into the structural basis for KV7.1 modulation by KCNE1. Recent evidence further suggests that KCNE2 may associate with the KV7.1–KCNE1 channel complex and modulate its current amplitude. Here we review recent studies in this area and discuss potential roles for multiple KCNEx subunits in IKs generation and modulation as well as the clinical relevance of the new information.