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Voltage sensors of a Na+ channel dissociate from the pore domain and form inter-channel dimers in the resting state

Author

Listed:
  • Ayumi Sumino

    (Kanazawa University
    Kanazawa University)

  • Takashi Sumikama

    (Kanazawa University)

  • Mikihiro Shibata

    (Kanazawa University
    Kanazawa University)

  • Katsumasa Irie

    (Wakayama Medical University)

Abstract

Understanding voltage-gated sodium (Nav) channels is significant since they generate action potential. Nav channels consist of a pore domain (PD) and a voltage sensor domain (VSD). All resolved Nav structures in different gating states have VSDs that tightly interact with PDs; however, it is unclear whether VSDs attach to PDs during gating under physiological conditions. Here, we reconstituted three different voltage-dependent NavAb, which is cloned from Arcobacter butzleri, into a lipid membrane and observed their structural dynamics by high-speed atomic force microscopy on a sub-second timescale in the steady state. Surprisingly, VSDs dissociated from PDs in the mutant in the resting state and further dimerized to form cross-links between channels. This dimerization would occur at a realistic channel density, offering a potential explanation for the facilitation of positive cooperativity of channel activity in the rising phase of the action potential.

Suggested Citation

  • Ayumi Sumino & Takashi Sumikama & Mikihiro Shibata & Katsumasa Irie, 2023. "Voltage sensors of a Na+ channel dissociate from the pore domain and form inter-channel dimers in the resting state," Nature Communications, Nature, vol. 14(1), pages 1-11, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43347-3
    DOI: 10.1038/s41467-023-43347-3
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    References listed on IDEAS

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    1. Jian Payandeh & Todd Scheuer & Ning Zheng & William A. Catterall, 2011. "The crystal structure of a voltage-gated sodium channel," Nature, Nature, vol. 475(7356), pages 353-358, July.
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