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Nat Commun. 2017 Dec 12;8(1):2077. doi: 10.1038/s41467-017-02262-0.

Voltage-gated sodium channels assemble and gate as dimers.

Author information

1
Heart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, 44109, USA. Jerome.clatot@gmail.com.
2
Heart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, 44109, USA.
3
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, 44106, USA.
4
Department of Physics, University of Illinois at Urbana-Champaign, Champaign, 61801, USA.
5
Cardiac Electrophysiology Research and Training Center, Faculty of Medicine, Chiang Mai University, Chiang Mai, 50200, Thailand.
6
L'Institut du Thorax, INSERM, CNRS, UNIV Nantes, Nantes, 44007, France.
7
Heart and Vascular Research Center, MetroHealth Campus, Case Western Reserve University, Cleveland, 44109, USA. isabelle.deschenes@case.edu.
8
Department of Physiology and Biophysics, Case Western Reserve University, Cleveland, OH, 44106, USA. isabelle.deschenes@case.edu.

Abstract

Fast opening and closing of voltage-gated sodium channels are crucial for proper propagation of the action potential through excitable tissues. Unlike potassium channels, sodium channel α-subunits are believed to form functional monomers. Yet, an increasing body of literature shows inconsistency with the traditional idea of a single α-subunit functioning as a monomer. Here we demonstrate that sodium channel α-subunits not only physically interact with each other but they actually assemble, function and gate as a dimer. We identify the region involved in the dimerization and demonstrate that 14-3-3 protein mediates the coupled gating. Importantly we show conservation of this mechanism among mammalian sodium channels. Our study not only shifts conventional paradigms in regard to sodium channel assembly, structure, and function but importantly this discovery of the mechanism involved in channel dimerization and biophysical coupling could open the door to new approaches and targets to treat and/or prevent sodium channelopathies.

PMID:
29233994
PMCID:
PMC5727259
DOI:
10.1038/s41467-017-02262-0
[Indexed for MEDLINE]
Free PMC Article

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