Voltage-gated ion channels and gating modifier toxins

William A. Catterall, Sandrine Cestèle, Vladimir Yarov-Yarovoy, Frank H. Yu, Keiichi Konoki, Todd Scheuer

Research output: Contribution to journalArticle

430 Scopus citations

Abstract

Voltage-gated sodium, calcium, and potassium channels generate electrical signals required for action potential generation and conduction and are the molecular targets for a broad range of potent neurotoxins. These channels are built on a common structural motif containing six transmembrane segments and a pore loop. Their pores are formed by the S5/S6 segments and the pore loop between them, and they are gated by bending of the S6 segments at a hinge glycine or proline residue. The voltage sensor domain consists of the S1-S4 segments, with positively charged residues in the S4 segment serving as gating charges. The diversity of toxin action on these channels is illustrated by sodium channels, which are the molecular targets for toxins that act at six or more distinct receptor sites on the channel protein. Both hydrophilic low molecular weight toxins and larger polypeptide toxins physically block the pore and prevent sodium conductance. Hydrophobic alkaloid toxins and related lipid-soluble toxins act at intramembrane sites and alter voltage-dependent gating of sodium channels via an allosteric mechanism. In contrast, polypeptide toxins alter channel gating by voltage-sensor trapping through binding to extracellular receptor sites, and this toxin interaction has now been modeled at the atomic level for a β-scorpion toxin. The voltage-sensor trapping mechanism may be a common mode of action for polypeptide gating modifier toxins acting on all of the voltage-gated ion channels.

Original languageEnglish (US)
Pages (from-to)124-141
Number of pages18
JournalToxicon
Volume49
Issue number2
DOIs
StatePublished - Feb 2007
Externally publishedYes

Keywords

  • Anemone toxins
  • Batrachotoxin
  • Conotoxins
  • Insect toxins
  • Neurotoxins
  • Saxitoxin
  • Scorpion toxins
  • Sodium channel
  • Tetrodotoxin
  • Toxin receptor sites
  • Veratridine

ASJC Scopus subject areas

  • Toxicology

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  • Cite this

    Catterall, W. A., Cestèle, S., Yarov-Yarovoy, V., Yu, F. H., Konoki, K., & Scheuer, T. (2007). Voltage-gated ion channels and gating modifier toxins. Toxicon, 49(2), 124-141. https://doi.org/10.1016/j.toxicon.2006.09.022