A gating hinge in Na+ channels: A molecular switch for electrical signaling

Yong Zhao, Vladimir Yarov-Yarovoy, Todd Scheuer, William A. Catterall

Research output: Contribution to journalArticle

115 Scopus citations

Abstract

Voltage-gated sodium channels are members of a large family with similar pore structures. The mechanism of opening and closing is unknown, but structural studies suggest gating via bending of the inner pore helix at a glycine hinge. Here we provide functional evidence for this gating model for the bacterial sodium channel NaChBac. Mutation of glycine 219 to proline, which would strongly favor bending of the α helix, greatly enhances activation by shifting its voltage dependence -51 mV and slowing deactivation by 2000-fold. The mutation also slows voltage-dependent inactivation by 1200-fold. The effects are specific because substitutions of proline at neighboring positions and substitutions of other amino acids at position 219 have much smaller functional effects. Our results fit a model in which concerted bending at glycine 219 in the S6 segments of NaChBac serves as a gating hinge. This gating motion may be conserved in most members of this large ion channel protein family.

Original languageEnglish (US)
Pages (from-to)859-865
Number of pages7
JournalNeuron
Volume41
Issue number6
DOIs
StatePublished - Mar 25 2004
Externally publishedYes

ASJC Scopus subject areas

  • Neuroscience(all)

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