Format

Send to

Choose Destination
Nat Commun. 2014 Mar 12;5:3420. doi: 10.1038/ncomms4420.

Evolutionarily conserved intracellular gate of voltage-dependent sodium channels.

Author information

1
1] Department of Neuroscience, University of Wisconsin, Madison, Wisconsin 53706, USA [2] Molecular Pharmacology Graduate Program, University of Wisconsin, Madison, Wisconsin 53706, USA.
2
Department of Neuroscience, University of Wisconsin, Madison, Wisconsin 53706, USA.
3
Molecular Neurophysiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.

Abstract

Members of the voltage-gated ion channel superfamily (VGIC) regulate ion flux and generate electrical signals in excitable cells by opening and closing pore gates. The location of the gate in voltage-gated sodium channels, a founding member of this superfamily, remains unresolved. Here we explore the chemical modification rates of introduced cysteines along the S6 helix of domain IV in an inactivation-removed background. We find that state-dependent accessibility is demarcated by an S6 hydrophobic residue; substituted cysteines above this site are not modified by charged thiol reagents when the channel is closed. These accessibilities are consistent with those inferred from open- and closed-state structures of prokaryotic sodium channels. Our findings suggest that an intracellular gate composed of a ring of hydrophobic residues is not only responsible for regulating access to the pore of sodium channels, but is also a conserved feature within canonical members of the VGIC superfamily.

PMID:
24619022
PMCID:
PMC3959192
DOI:
10.1038/ncomms4420
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center