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

Author

Listed:
  • Rene Barro-Soria

    (Miller School of Medicine, University of Miami)

  • Santiago Rebolledo

    (Miller School of Medicine, University of Miami)

  • Sara I. Liin

    (Miller School of Medicine, University of Miami)

  • Marta E. Perez

    (Miller School of Medicine, University of Miami)

  • Kevin J. Sampson

    (College of Physicians and Surgeons of Columbia University)

  • Robert S. Kass

    (College of Physicians and Surgeons of Columbia University)

  • H. Peter Larsson

    (Miller School of Medicine, University of Miami)

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.

Suggested Citation

  • Rene Barro-Soria & Santiago Rebolledo & Sara I. Liin & Marta E. Perez & Kevin J. Sampson & Robert S. Kass & H. Peter Larsson, 2014. "KCNE1 divides the voltage sensor movement in KCNQ1/KCNE1 channels into two steps," Nature Communications, Nature, vol. 5(1), pages 1-12, September.
    • Handle: RePEc:nat:natcom:v:5:y:2014:i:1:d:10.1038_ncomms4750
    DOI: 10.1038/ncomms4750
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