Using voltage-sensor toxins and their molecular targets to investigate NaV1.8 gating

John Gilchrist, Frank Bosmans

Research output: Contribution to journalReview articlepeer-review

Abstract

Voltage-gated sodium (NaV) channel gating is a complex phenomenon which involves a distinct contribution of four integral voltage-sensing domains (VSDI, VSDII, VSDIII and VSDIV). Utilizing accrued pharmacological and structural insights, we build on an established chimera approach to introduce animal toxin sensitivity in each VSD of an acceptor channel by transferring in portable S3b–S4 motifs from the four VSDs of a toxin-susceptible donor channel (NaV1.2). By doing so, we observe that in NaV1.8, a relatively unexplored channel subtype with distinctly slow gating kinetics, VSDI–III participate in channel opening whereas VSDIV can regulate opening as well as fast inactivation. These results illustrate the effectiveness of a pharmacological approach to investigate the mechanism underlying gating of a mammalian NaV channel complex. (Figure presented.).

Original languageEnglish (US)
Pages (from-to)1863-1872
Number of pages10
JournalJournal of Physiology
Volume596
Issue number10
DOIs
StatePublished - May 15 2018

Keywords

  • Na1.8
  • S3b-S4 motif
  • gating
  • scorpion toxin
  • spider toxin
  • voltage-sensing domain

ASJC Scopus subject areas

  • Physiology

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