Tetrodotoxin (anhydrotetrodotoxin 4-epitetrodotoxin, tetrodonic acid, TTX) is a potent
neurotoxin with no known antidote, which blocks
action potentials in
nerves by binding to the
pores of the
voltage-gated, fast
sodium channels in
nerve cell membranes.
[1] The
binding site of this toxin is located at the pore opening of the voltage-gated Na
+ channel. Its name derives from
Tetraodontiformes, the name of the order that includes the
pufferfish,
porcupinefish,
ocean sunfish or mola, and
triggerfish, several species of which carry the toxin. Although tetrodotoxin was discovered in these fish and found in several other animals (e.g.,
Blue-ringed Octopus,
Rough-skinned newt), it is actually the product of certain
bacteria such as
Pseudoalteromonas tetraodonis, certain species of
Pseudomonas and
Vibrio, as well as some others.
Its mechanism was discovered in the early 1960s by Toshio Narahashi working at Duke University.
Tetrodotoxin has also been isolated from widely differing animal species, including western newts of the genus Taricha (where it was termed "tarichatoxin"), parrotfish, toads of the genus Atelopus, several species of blue-ringed octopuses of the genus Hapalochlaena (where it was called "maculotoxin"), several starfish, an angelfish, a polyclad flatworm, several species of Chaetognatha (arrow worms), several nemerteans (ribbonworms) and several species of xanthid crabs. The toxin is variously used as a defensive biotoxin to ward off predation, or as both a defensive and predatory venom (the octopodes, chaetognaths and ribbonworms). Tarichatoxin and maculotoxin were shown to be identical to tetrodotoxin in 1964 and 1978, respectively. Recent evidence has shown the toxin to be produced by bacteria within blue-ringed octopuses.[2] The most common source of bacteria associated with TTX production is 'Vibrio' bacteria, with Vibrio alginolyticus being the most common species. Pufferfish,[3] chaetognaths,[4] and nemerteans[5] have been shown to contain Vibrio alginolyticus and TTX.
Tetrodotoxin binds to what is known as site 1 of the fast voltage-gated sodium channel. Site 1 is located at the extracellular pore opening of the ion channel. The binding of any molecules to this site will temporarily disable the function of the ion channel. Saxitoxin and several of the conotoxins also bind the same site.
