Referenced in: none

Automatically associated channels: Kv10.1

Title: Evolutionarily conserved intracellular gate of voltage-dependent sodium channels.

Authors: Kevin Oelstrom, Marcel P Goldschen-Ohm, Miguel Holmgren, Baron Chanda

Journal, date & volume: Nat Commun, 2014 , 5, 3420

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24619022

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.