Tetrodotoxin (TTX) is the poison that makes puffer fish so dangerous to eat. Tetrodotoxin causes paralysis by selectively blocking sodium ion channels in the membranes of excitable cells (that is - neurons). As a result, nerve impulses cannot propagate and death is inevitable.

Tetrodotoxin binds tightly and physically blocks the channel, preventing sodium currents from passing through the membrane. Only 100 molecules of toxin will completely deplete activity of a one square micron of tissue. Tetrodotoxin is also used in neurophysiological experiments to study the role of sodium channels in nerve behavior.

See also: neurotoxin

A minor correction -- death is not actually "inevitable." The tetrodotoxin molecule does not block the Sodium channel indefinitely. If you can stay alive for 24 hours (through luck or a forced-breathing machine), the molecule will un-bind and you will be fine.

That said, it's heinous stuff, 10,000 times more lethal than cyanide, per gram. 25 minutes after exposure it begins to paralyze its victims, leaving the brain fully aware of what's happening. Death usually results within a few hours from suffocation or heart failure. TTX is one of few neurotoxins that are not protein-based. It is found in a wide array of animals that are related only very distantly. The explanation may be that it is produced by a microorganism that lives in symbiosis with each of these creatures.

Tetrodotoxin is a neurotoxin most famously found in pufferfish (especially those in Tetraodontidae). In general, the toxin (henceforth referred to by its acronym, TTX) is found in the liver, intestines, ovaries, and skin, but not muscle, of the pufferfish - but, as with any rule, there are exceptions. I don't recommend that you try to prepare fugu based on what you read here.

Other, lesser-known producers of TTX include frogs of the genus Atelopus, octopi of the genus Hapalochlaena, several species of marine fish and crabs, and two mollusks called the trumpet shell and ivory shell found in Japan. TTX is also found in newts, where it used to be called Tarichatoxin.

The TTX molecule is an alkaloid. It contains a pyrimidine ring, a guanidine group, and a few other fused rings. It mimics the sodium cation well enough to bind to the sodium channel in cell membranes. Where the channel binds sodium loosely for a nanosecond or two, it binds TTX very tightly, and for tens of seconds. The mechanism and toxicity are similar to that of saxitoxin, a poison found in shellfish. Sodium channels are necessary for nerve cells to conduct impulses, and for muscles to contract.

The first symptoms of poisoning usually occur within the first hour or so of ingesting the toxin. Numbness and paresthesia (tingling) occur in the lips and tongue, and then the face and extremities. The victim may feel lightheaded, or like they are floating. After that, symptoms will probably include nausea, vomiting, stomach pain, and headache. Afterwards, paralysis begins, which makes breathing difficult. Convulsions and arrythmia may occur toward the end. Time for the whole process, from ingestion to death: anywhere from 20 minutes to 8 hours.

Most cases of TTX poisoning occur in Japan, where pufferfish (fugu) is a more popular food item than in other parts of the world. Fugu chefs must be licensed by the government, but even so, something like 20-100 people die each year from eating fugu. (The rate may be even lower in recent years; also, gn0sis tells me that most deaths are from fugu that was not prepared by licensed chefs.) In most other parts of the world, fugu and TTX poisoning are very rare.

TTX is one of the most toxic known biological substances. Less than a milliliter can kill an adult human. According to William H. Light,

"Weight-for-weight, tetrodotoxin is ten times as deadly as the venom of the many-banded krait of Southeast Asia. It is 10 to 100 times as lethal as black widow spider venom (depending upon the species) when administered to mice, and more than 10,000 times deadlier than cyanide."

Animals that produce TTX are also resistant to it - their sodium channels are slightly mutated so that sodium binds correctly but TTX is unable to bind. There is evidence that the TTX is produced by symbiotic bacteria living inside the animal, rather than by the animal itself. Most of these animals use TTX defensively (ie, as a poison), but the blue-ringed octopus actually uses it as a venom that it injects into its prey.

References and further reading:

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