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The chemical basis for electrical signaling

Nature Chemical Biology volume 13, pages 455–463 (2017)Cite this article

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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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Figure 1: Overall architecture of voltage-gated sodium, calcium, and potassium channels.
Figure 2: Structure of the voltage-sensing module of NaVAb.
Figure 3: Structural models of resting and activated states of voltage-sensing modules.
Figure 4: Structural model of conformational changes during channel activation and pore opening.
Figure 5: Chemical mechanism of ion permeation and selectivity of NaV and CaV channels with structural models of their ion selectivity filters with ions bound.
Figure 6: Conformational changes in the pore associated with slow inactivation.

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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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Catterall, W., Wisedchaisri, G. & Zheng, N. The chemical basis for electrical signaling. Nat Chem Biol 13, 455–463 (2017). https://doi.org/10.1038/nchembio.2353

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