Molecular basis of ion permeability in a voltage-gated sodium channel

Claire E. Naylor; Claire Bagnéris; Paul G. Decaen; Altin Sula; Antonella Scaglione; David E. Clapham; B. Wallace

doi:10.15252/embj.201593285

Molecular basis of ion permeability in a voltage-gated sodium channel

Claire E. Naylor, Claire Bagnéris, Paul G. Decaen, Altin Sula, Antonella Scaglione, David E. Clapham, B. Wallace^*

^*Corresponding author for this work

Pharmacology

Research output: Contribution to journal › Article › peer-review

88 Scopus citations

Abstract

Voltage-gated sodium channels are essential for electrical signalling across cell membranes. They exhibit strong selectivities for sodium ions over other cations, enabling the finely tuned cascade of events associated with action potentials. This paper describes the ion permeability characteristics and the crystal structure of a prokaryotic sodium channel, showing for the first time the detailed locations of sodium ions in the selectivity filter of a sodium channel. Electrostatic calculations based on the structure are consistent with the relative cation permeability ratios (Na⁺ ≈ Li⁺ ≫ K⁺, Ca²⁺, Mg²⁺) measured for these channels. In an E178D selectivity filter mutant constructed to have altered ion selectivities, the sodium ion binding site nearest the extracellular side is missing. Unlike potassium ions in potassium channels, the sodium ions in these channels appear to be hydrated and are associated with side chains of the selectivity filter residues, rather than polypeptide backbones.

Original language	English (US)
Pages (from-to)	820-830
Number of pages	11
Journal	EMBO Journal
Volume	35
Issue number	8
DOIs	https://doi.org/10.15252/embj.201593285
State	Published - Apr 15 2016

Funding

We thank Dr. Ambrose Cole (Birkbeck College) for help with crystallographic data collection and the beamline scientists at the Diamond Light Source, UK, Soleil, France, and the ESRF, France. This work was supported by grants (BB/H01070X, BB/L006790 and BB/L02625) from the UK Biotechnology and Biological Science Research Council (BBSRC) to BAW. CEN was supported, in part, by a grant from Pfizer Neusentis (to BAW). PGD was supported by National Institutes of Health Grant T32-HL007572 and NIH Pathway to Independence (PI) Award (K99/R00) from the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). The crystallographic research leading to these results has received funding from the European Community's Seventh Framework Programme (FP7/2007-2013) under BioStruct-X (grant agreement No283570).

Keywords

crystal structure
electrophysiology
ion permeability
sodium channel

ASJC Scopus subject areas

General Immunology and Microbiology
General Biochemistry, Genetics and Molecular Biology
Molecular Biology
General Neuroscience

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AU - Clapham, David E.

AU - Wallace, B.

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Molecular basis of ion permeability in a voltage-gated sodium channel

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Keywords

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