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Structure of Sodium and Calcium Channels with Ligands

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Abstract

Sodium and calcium channels play fundamental roles in the physiology of excitable cells. These channels are targets for various natural toxins, synthetic drugs and insecticides. Genetic mutations in sodium and calcium channels are associated with hereditary diseases such as cardiac arrhythmias, epilepsy, myotonia, hyperalgesia and hypoalgesia. It is not surprising that the development of selective modulators of sodium and calcium channels is an important task of neuropharmacology. In recent years, crystal and cryo-electron microscopic structures of sodium and calcium channels and their complexes with toxins and drugs have been published. In these studies, structural explanations are proposed for the numerous experimental data accumulated in previous decades. In the current review, experimental structures and theoretical models of sodium and calcium channels with toxins and drugs are considered. The possible role of current-carrying cations and their binding sites in the action of some ligands is discussed.

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Abbreviations

BTX:

batrachotoxin;

CavAb:

calcium-selective mutant of the NavAb channel;

Cav1.x:

L-type calcium channels;

EM:

electron microscopy;

µCTX:

µ-conotoxin;

Nav1.x:

eukaryotic voltage-gated sodium channels;

NavAb and NavMs:

prokaryotic voltage-gated sodium channels;

NavPaS:

cockroach sodium channel;

PD:

pore domain;

PyR1 and PyR2:

receptors of pyrethroid insecticides;

SI, SII and SIII :

binding sites of current-carrying ions in the outer pore of sodium and calcium channels;

STX:

saxitoxin;

TTX:

tetrodotoxin;

VSD:

voltage-sensing domain;

VTD:

veratridine

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This work was supported by the Ministry of Science in Higher Education for the Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences.

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  1. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, Petersburg, Russia

    B. S. Zhorov

  2. McMaster University, Hamilton, Canada

    B. S. Zhorov

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Russian Text © The Author(s), 2021, published in Rossiiskii Fiziologicheskii Zhurnal imeni I.M. Sechenova, 2021, Vol. 107, Nos. 4–5, pp. 417–435https://doi.org/10.31857/S0869813921040178.

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Zhorov, B.S. Structure of Sodium and Calcium Channels with Ligands. J Evol Biochem Phys 57, 337–353 (2021). https://doi.org/10.1134/S0022093021020150

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