Point-mutations related to the loss of batrachotoxin binding abolish the grayanotoxin effect in Na(+) channel isoforms

Jpn J Physiol. 1999 Oct;49(5):457-61. doi: 10.2170/jjphysiol.49.457.

Abstract

The effect of grayanotoxin (GTX) on site-specific mutants of the alpha-subunit of rat skeletal muscle Na(+) channels (micro1) (micro1-I433K, micro1-N434K and micro1-L437K), which are resistant to batrachotoxin (BTX) (Wang and Wang (1998) Proc Natl Acad Sci USA, 95, 2653-2658) was studied using a whole-cell patch-clamp method. The GTX modification of the Na(+) channels was detected as a characteristic-sustained Na(+) current flow with repetitive pulses. We also studied the GTX action on mutants of the alpha-subunit of rat heart Na(+) channels (RH1) (RH1-V406K and RH1-L410K) which match with micro1-I433 and micro1-L437. All the mutants lost their sensitivity to GTX. This finding indicates that GTX may share a binding site with BTX in transmembrane segment I-S6 of two different Na(+) channel isoforms, micro1 and RH1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Batrachotoxins / metabolism
  • Batrachotoxins / pharmacology*
  • DNA Primers
  • Diterpenes / metabolism
  • Diterpenes / pharmacology*
  • Ion Channel Gating / drug effects
  • Ion Channel Gating / genetics
  • Isomerism
  • Muscle, Skeletal / chemistry
  • Mutagenesis, Site-Directed / physiology
  • Patch-Clamp Techniques
  • Point Mutation*
  • Rats
  • Sodium Channels / chemistry
  • Sodium Channels / genetics*
  • Sodium Channels / metabolism*

Substances

  • Batrachotoxins
  • DNA Primers
  • Diterpenes
  • Sodium Channels
  • grayanotoxin II