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Inactivation of KCNQ1 potassium channels reveals dynamic coupling between voltage sensing and pore opening

Author

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  • Panpan Hou

    (Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Diseases, Cardiac Bioelectricity and Arrhythmia Center, Washington University in St Louis)

  • Jodene Eldstrom

    (Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia)

  • Jingyi Shi

    (Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Diseases, Cardiac Bioelectricity and Arrhythmia Center, Washington University in St Louis)

  • Ling Zhong

    (Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Diseases, Cardiac Bioelectricity and Arrhythmia Center, Washington University in St Louis)

  • Kelli McFarland

    (Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Diseases, Cardiac Bioelectricity and Arrhythmia Center, Washington University in St Louis)

  • Yuan Gao

    (Tencent AI Lab)

  • David Fedida

    (Department of Anesthesiology, Pharmacology and Therapeutics, University of British Columbia)

  • Jianmin Cui

    (Department of Biomedical Engineering, Center for the Investigation of Membrane Excitability Diseases, Cardiac Bioelectricity and Arrhythmia Center, Washington University in St Louis)

Abstract

In voltage-activated ion channels, voltage sensor (VSD) activation induces pore opening via VSD-pore coupling. Previous studies show that the pore in KCNQ1 channels opens when the VSD activates to both intermediate and fully activated states, resulting in the intermediate open (IO) and activated open (AO) states, respectively. It is also well known that accompanying KCNQ1 channel opening, the ionic current is suppressed by a rapid process called inactivation. Here we show that inactivation of KCNQ1 channels derives from the different mechanisms of the VSD-pore coupling that lead to the IO and AO states, respectively. When the VSD activates from the intermediate state to the activated state, the VSD-pore coupling has less efficacy in opening the pore, producing inactivation. These results indicate that different mechanisms, other than the canonical VSD-pore coupling, are at work in voltage-dependent ion channel activation.

Suggested Citation

  • Panpan Hou & Jodene Eldstrom & Jingyi Shi & Ling Zhong & Kelli McFarland & Yuan Gao & David Fedida & Jianmin Cui, 2017. "Inactivation of KCNQ1 potassium channels reveals dynamic coupling between voltage sensing and pore opening," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01911-8
    DOI: 10.1038/s41467-017-01911-8
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    Cited by:

    1. Katrien Willegems & Jodene Eldstrom & Efthimios Kyriakis & Fariba Ataei & Harutyun Sahakyan & Ying Dou & Sophia Russo & Filip Petegem & David Fedida, 2022. "Structural and electrophysiological basis for the modulation of KCNQ1 channel currents by ML277," Nature Communications, Nature, vol. 13(1), pages 1-17, December.

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