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

  • Nat Commun. 2014 Apr 28:5:3750. doi: 10.1038/ncomms4750.
Rene Barro-Soria  1 ,  Santiago Rebolledo  1 ,  Sara I Liin  1 ,  Marta E Perez  1 ,  Kevin J Sampson  2 ,  Robert S Kass  2 ,  H Peter Larsson  1
Affiliations
  • 1. Department of Physiology and Biophysics, Miller School of Medicine, University of Miami, Miami, Florida 33136, USA.
  • 2. Department of Pharmacology, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
PMID: 24769622 DOI: 10.1038/ncomms4750
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.

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