Answer: Tetrodotoxin (TTX) is a voltage-gated sodium channel inhibitor.
TTX is a large molecule neurotoxin that is produced by symbiotic bacteria found in pufferfish as well as other aquatic species and amphibians.
Tetrodotoxin blocks the sodium channels that transmit neuronal signals down an axon.
Exposure to tiny amounts of TTX is lethal in humans. Within hours, symptoms such as numbness, seizures, and loss of respiration occur. There is no antidote to TTX, but patients can be placed on ventilators until the toxin is flushed out of the system.
Pufferfish is a culinary delicacy in Japan. There is a high incidence of tetrodotoxin poisoning occurring in Japan annually.
The most common misconception about tetrodotoxin is that is not produced by the pufferfish itself. The puffer fish is a host to one of several strains of bacteria, including Vibrio, Aeromonas, and Pseudomonas. These bacteria are responsible for producing the actual toxin. The toxin accumulates in various organs of the pufferfish, including the skin, liver, eyes, ovaries, and muscle tissue.
The toxin is extremely dangerous, especially when purified. The median lethal dose, or LD50, is around 300 micrograms per kilogram of weight (ug/kg). However, the prognosis is good when the poisoning is detected early. A proper diagnosis based off recent consumption history and observed symptoms allows for the doctors to treat the patient appropriately.
The first 24 hours of exposure to the poison are the most critical. Positive pressure into the airways can overcome the paralysis that comes from a lack of nervous signaling into the lungs. Additional symptoms can be treated directly, but there is no known drug that can shorten the time span of TTX poisoning. The action of tetrodotoxin on the voltage gated sodium channels are essentially irreversible, as only the internalization and degradation of the receptors will end the effects of the poison.
However, there is a possible line of research regarding methods to decrease the symptoms on initial exposure to tetrodotoxin. Dr Victor Rivera in the article "Prophylaxis and treatment with a monoclonal antibody of tetrodotoxin poisoning in mice" demonstrated that treatment with a monoclonal antibody was able to decrease the lethality of tetrodotoxin poisoning in mice. The monoclonal antibody would likely bind to the TTX in a competitive manner, thus decreasing the amount of active TTX in the body. Less TTX in the system would mean that neuronal innervation of the diaphragm may remain high enough to prevent the subjects from dying.
