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

Research output: Contribution to journalArticlepeer-review

59 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 languageEnglish (US)
Pages (from-to)820-830
Number of pages11
JournalEMBO Journal
Volume35
Issue number8
DOIs
StatePublished - Apr 15 2016

Keywords

  • crystal structure
  • electrophysiology
  • ion permeability
  • sodium channel

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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