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


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.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

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