Site-3 toxins and cardiac sodium channels

Toxicon. 2007 Feb;49(2):181-93. doi: 10.1016/j.toxicon.2006.09.017. Epub 2006 Sep 27.


Site-3 toxins are small polypeptide venoms from scorpions, sea anemones, and spiders that bind with a high specificity to the extracellular surface of voltage-gated Na channels. After binding to a site near the S4 segment in domain IV the toxin causes disruption of the normal fast inactivation transition resulting in a marked prolongation of the action potentials of excitable tissues including those of cardiac and skeletal muscle and nerve. In this review we discuss the specific binding interactions between residues of the toxin and those of the Na channel, and the specific modification of Na channel kinetic behavior leading to a change in fast inactivation focusing on interactions deduced primarily from the study of sea anemone toxins and the cardiac Na channel (Na(V)1.5). We also illustrate the usefulness of site-3 toxins in the study of altered Na channel behavior by drug-modification.

Publication types

  • Review

MeSH terms

  • Animals
  • Cnidarian Venoms / pharmacology
  • Humans
  • Ion Channel Gating* / drug effects
  • Ion Channel Gating* / physiology
  • NAV1.3 Voltage-Gated Sodium Channel
  • Scorpion Venoms / pharmacology
  • Sea Anemones
  • Sodium Channels / drug effects*
  • Spider Venoms / pharmacology
  • Venoms / pharmacology*
  • Voltage-Gated Sodium Channel beta-3 Subunit


  • Cnidarian Venoms
  • NAV1.3 Voltage-Gated Sodium Channel
  • SCN3A protein, human
  • SCN3B protein, human
  • Scorpion Venoms
  • Sodium Channels
  • Spider Venoms
  • Venoms
  • Voltage-Gated Sodium Channel beta-3 Subunit