The tetrodotoxin binding site is within the outer vestibule of the sodium channel

Mar Drugs. 2010 Feb 1;8(2):219-34. doi: 10.3390/md8020219.


Tetrodotoxin and saxitoxin are small, compact asymmetrical marine toxins that block voltage-gated Na channels with high affinity and specificity. They enter the channel pore's outer vestibule and bind to multiple residues that control permeation. Radiolabeled toxins were key contributors to channel protein purification and subsequent cloning. They also helped identify critical structural elements called P loops. Spacial organization of their mutation-identified interaction sites in molecular models has generated a molecular image of the TTX binding site in the outer vestibule and the critical permeation and selectivity features of this region. One site in the channel's domain I P loop determines affinity differences in mammalian isoforms.

Keywords: Na channels; marine toxins; molecular modeling.

Publication types

  • Review

MeSH terms

  • Binding Sites
  • Cloning, Molecular
  • Ion Channel Gating
  • Models, Molecular
  • Mutation
  • Sodium Channel Blockers / pharmacology
  • Sodium Channels / chemistry*
  • Sodium Channels / genetics
  • Sodium Channels / metabolism
  • Tetrodotoxin / metabolism*
  • Tetrodotoxin / pharmacology


  • Sodium Channel Blockers
  • Sodium Channels
  • Tetrodotoxin