Referenced in: none

Automatically associated channels: Kv7.1 , Slo1

Title: KCNE1 divides the voltage sensor movement in KCNQ1/KCNE1 channels into two steps.

Authors: René Barro-Soria, Santiago Rebolledo, Sara I Liin, Marta E Perez, Kevin J Sampson, Robert S Kass, H Peter Larsson

Journal, date & volume: Nat Commun, 2014 , 5, 3750

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24769622

Abstract
The functional properties of KCNQ1 channels are highly dependent on associated KCNE-β subunits. Mutations in KCNQ1 or KCNE subunits can cause congenital channelopathies, such as deafness, cardiac arrhythmias and epilepsy. The mechanism by which KCNE1-β subunits slow the kinetics of KCNQ1 channels is a matter of current controversy. Here we show that KCNQ1/KCNE1 channel activation occurs in two steps: first, mutually independent voltage sensor movements in the four KCNQ1 subunits generate the main gating charge movement and underlie the initial delay in the activation time course of KCNQ1/KCNE1 currents. Second, a slower and concerted conformational change of all four voltage sensors and the gate, which opens the KCNQ1/KCNE1 channel. Our data show that KCNE1 divides the voltage sensor movement into two steps with widely different voltage dependences and kinetics. The two voltage sensor steps in KCNQ1/KCNE1 channels can be pharmacologically isolated and further separated by a disease-causing mutation.