Molecular determinant of Nav1.8 sodium channel resistance to the venom from the scorpion Leiurus quinquestriatus hebraeus

Carl Y. Saab, Theodore R. Cummins, Sulayman D. Dib-Hajj, Stephen G. Waxman

Research output: Contribution to journalArticle

17 Scopus citations

Abstract

The scorpion venom from Leiurus quinquestriatus (LQTX) alters the kinetics of tetrodotoxin (TTX)-sensitive channels such as the skeletal muscle sodium channel Nav1.4. In this study, we tested the effects of LQTX on the TTX-resistant sodium current generated by Nav1.8 channels in sensory neurons. Nav1.8 current was found to be resistant to LQTX, whereas LQTX slowed inactivation of the current generated by Nav1.4 and induced a persistent current. LQTX has been shown to bind the S3-S4 linker of domain four (D4S3-S4) of rat brain Nav1.2 sodium channels. Sequence analysis shows that the D4S3-S4 linker is longer in Nav1.8 than in Nav1.4 by four amino acids: Serine; Leucine; Glutamic acid; and Aspargine (SLEN). Nav1.4-SLEN, a chimera construct carrying SLEN at the analogous position in the D4S3-S4 linker, was also found to be resistant to LQTX. Therefore, we conclude that the tetrapeptide SLEN at the D4S3-S4 linker region is sufficient to make Nav1.8 resistant to LQTX.

Original languageEnglish (US)
Pages (from-to)79-82
Number of pages4
JournalNeuroscience Letters
Volume331
Issue number2
DOIs
StatePublished - Oct 11 2002
Externally publishedYes

Keywords

  • Leiurus quinquestriatus toxin
  • Na1.4-Serine, leucine, glutamic acid and aspargine
  • Na1.8
  • Sodium channel
  • Tetrodotoxin

ASJC Scopus subject areas

  • Neuroscience(all)

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