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Molecular biology and biophysical properties of ion channel gating pores

Published online by Cambridge University Press:  10 November 2014

Adrien Moreau ,
Pascal Gosselin-Badaroudine  and
Mohamed Chahine
Adrien Moreau
Affiliation:
Centre de recherche de l'institut universitaire en santé mentale de Québec, Quebec City, QC, CanadaG1J 2G3
Pascal Gosselin-Badaroudine
Affiliation:
Centre de recherche de l'institut universitaire en santé mentale de Québec, Quebec City, QC, CanadaG1J 2G3
Mohamed Chahine*
Affiliation:
Centre de recherche de l'institut universitaire en santé mentale de Québec, Quebec City, QC, CanadaG1J 2G3 Department of Medicine, Université Laval, Quebec City, QC, CanadaG1K 7P4
*
*Author for correspondence: Mohamed Chahine, Centre de recherche, Institut universitaire en santé mentale de Québec 2601 chemin de la Canardière, Quebec City, QC, CanadaG1J 2G3. Tel: 1-418-663-5747, ext. 4723; Fax: 1-418-663-8756; Email: mohamed.chahine@phc.ulaval.ca
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Abstract

The voltage sensitive domain (VSD) is a pivotal structure of voltage-gated ion channels (VGICs) and plays an essential role in the generation of electrochemical signals by neurons, striated muscle cells, and endocrine cells. The VSD is not unique to VGICs. Recent studies have shown that a VSD regulates a phosphatase. Similarly, Hv1, a voltage-sensitive protein that lacks an apparent pore domain, is a self-contained voltage sensor that operates as an H+ channel.

VSDs are formed by four transmembrane helices (S1–S4). The S4 helix is positively charged due to the presence of arginine and lysine residues. It is surrounded by two water crevices that extend into the membrane from both the extracellular and intracellular milieus. A hydrophobic septum disrupts communication between these water crevices thus preventing the permeation of ions. The septum is maintained by interactions between the charged residues of the S4 segment and the gating charge transfer center. Mutating the charged residue of the S4 segment allows the water crevices to communicate and generate gating pore or omega pore. Gating pore currents have been reported to underlie several neuronal and striated muscle channelopathies. Depending on which charged residue on the S4 segment is mutated, gating pores are permeant either at depolarized or hyperpolarized voltages. Gating pores are cation selective and seem to converge toward Eisenmann's first or second selectivity sequences. Most gating pores are blocked by guanidine derivatives as well as trivalent and quadrivalent cations. Gating pores can be used to study the movement of the voltage sensor and could serve as targets for novel small therapeutic molecules.

Type
Review Article
Information
Quarterly Reviews of Biophysics , Volume 47 , Issue 4 , November 2014 , pp. 364 - 388
Copyright
Copyright © Cambridge University Press 2014 

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