Voltage-gated sodium channels assemble and gate as dimers

Jérôme Clatot (), Malcolm Hoshi, Xiaoping Wan, Haiyan Liu, Ankur Jain, Krekwit Shinlapawittayatorn, Céline Marionneau, Eckhard Ficker, Taekjip Ha and Isabelle Deschênes ()
Additional contact information
Jérôme Clatot: Case Western Reserve University
Malcolm Hoshi: Case Western Reserve University
Xiaoping Wan: Case Western Reserve University
Haiyan Liu: Case Western Reserve University
Ankur Jain: University of Illinois at Urbana-Champaign
Krekwit Shinlapawittayatorn: Case Western Reserve University
Céline Marionneau: L’Institut du Thorax, INSERM, CNRS, UNIV Nantes
Eckhard Ficker: Case Western Reserve University
Taekjip Ha: University of Illinois at Urbana-Champaign
Isabelle Deschênes: Case Western Reserve University

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: 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.

Date: 2017
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-017-02262-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-02262-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-017-02262-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().