Review Article | Published:

The chemical basis for electrical signaling

Nature Chemical Biology volume 13, pages 455463 (2017) | Download Citation

Abstract

Electrical signals generated by minute currents of ions moving across cell membranes are central to all rapid processes in biology. Initiation and propagation of electrical signals requires voltage-gated sodium (NaV) and calcium (CaV) channels. These channels contain a tetramer of membrane-bound subunits or domains comprising a voltage sensor and a pore module. Voltage-dependent activation occurs as membrane depolarization drives outward movements of positive gating changes in the voltage sensor via a sliding-helix mechanism, which leads to a conformational change in the pore module that opens its intracellular activation gate. A unique negatively charged site in the selectivity filter conducts hydrated Na+ or Ca2+ rapidly and selectively. Ion conductance is terminated by voltage-dependent inactivation, which causes asymmetric pore collapse. This Review focuses on recent advances in structure and function of NaV and CaV channels that expand our current understanding of the chemical basis for electrical signaling mechanisms conserved from bacteria to humans.

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Acknowledgements

The research from the authors' laboratories reviewed here and preparation of this article were supported by NIH Research Grants R01 HL112808 and R01 HL117896 (W.A.C. and N.Z.), NIH Research Grant R01 NS15751 (W.A.C.), and the Howard Hughes Medical Institute (N.Z.).

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  1. Department of Pharmacology, University of Washington, Seattle, Washington, USA.

    • William A Catterall
    • , Goragot Wisedchaisri
    •  & Ning Zheng
  2. Howard Hughes Medical Institute, University of Washington, Seattle, Washington, USA.

    • Ning Zheng

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The authors declare no competing financial interests.

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Correspondence to William A Catterall.

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https://doi.org/10.1038/nchembio.2353

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