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Structural Models of Ligand-Bound Sodium Channels

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Voltage-gated Sodium Channels: Structure, Function and Channelopathies

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 246))

Abstract

X-ray and cryo-EM structures of tetrameric and pseudo-tetrameric P-loop channels are used to elaborate homology models of mammalian voltage-gated sodium channels with drugs and neurotoxins. Such models integrate experimental data, assist in planning new experiments, and may facilitate drug design. This chapter outlines sodium channel models with local anesthetics, anticonvulsants, and antiarrhythmics, which are used to manage pain and treat sodium channelopathies. Further summarized are sodium channel models with tetrodotoxin, mu-conotoxins, batrachotoxin, scorpion toxins, and insecticides. Possible involvement of sodium ions in the action of some ligands is discussed.

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Abbreviations

DDT:

Dichlorodiphenyltrichloroethane

EM:

Electron microscopy

LAs:

Local anesthetics

MC:

Monte Carlo

MCM:

MC minimization

MD:

Molecular dynamics

PyR:

Pyrethroid receptor

SCBIs:

Sodium channel blocker insecticides

STX:

Saxitoxin

TTX:

Tetrodotoxin

VSD:

Voltage-sensing domain

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Acknowledgments

This work was supported by grant 17-15-01292 from the Russian Science Foundation.

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Authors and Affiliations

  1. Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, ON, Canada

    Boris S. Zhorov

  2. I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, RAS, St. Petersburg, Russia

    Boris S. Zhorov

  3. Institute of Molecular Biology and Genetics, Almazov Federal Heart, Blood and Endocrinology Centre, St. Petersburg, Russia

    Boris S. Zhorov

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  1. Boris S. Zhorov
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Correspondence to Boris S. Zhorov .

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Editors and Affiliations

  1. CERVO Brain Research Center, Institut Universitaire en Santé Mentale, Quebec, Canada

    Mohamed Chahine

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Zhorov, B.S. (2017). Structural Models of Ligand-Bound Sodium Channels. In: Chahine, M. (eds) Voltage-gated Sodium Channels: Structure, Function and Channelopathies. Handbook of Experimental Pharmacology, vol 246. Springer, Cham. https://doi.org/10.1007/164_2017_44

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