Tetrodotoxin | EPFL Graph Search

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Tetrodotoxin (TTX) is a potent neurotoxin. Its name derives from Tetraodontiformes, an order that includes pufferfish, porcupinefish, ocean sunfish, and triggerfish; several of these species carry the toxin. Although tetrodotoxin was discovered in these fish and found in several other animals (e.g., in blue-ringed octopuses, rough-skinned newts, and moon snails), it is actually produced by certain infecting or symbiotic bacteria like Pseudoalteromonas, Pseudomonas, and Vibrio as well as other species found in animals. Although it produces thousands of intoxications annually and several deaths, it has shown efficacy for the treatment of cancer-related pain in phase II and III clinical trials. Tetrodotoxin is a sodium channel blocker. It inhibits the firing of action potentials in neurons by binding to the voltage-gated sodium channels in nerve cell membranes and blocking the passage of sodium ions (responsible for the rising phase of an action potential) into the neuron. This prevents the nervous system from carrying messages and thus muscles from contracting in response to nervous stimulation. Its mechanism of action, selective blocking of the sodium channel, was shown definitively in 1964 by Toshio Narahashi and John W. Moore at Duke University, using the sucrose gap voltage clamp technique. Apart from their bacterial species of most likely ultimate biosynthetic origin (see below), tetrodotoxin has been isolated from widely differing animal species, including: all octopuses and cuttlefish in small amounts, but specifically several species of the blue-ringed octopus, including Hapalochlaena maculosa (where it was called "maculotoxin"), various pufferfish species, certain angelfish, species of Nassarius gastropods, species of Naticidae (moon snails), several starfish, including Astropecten species, several species of xanthid crabs.

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Sodium channel

Sodium channels are integral membrane proteins that form ion channels, conducting sodium ions (Na+) through a cell's membrane. They belong to the superfamily of cation channels. They are classified into 2 types: In excitable cells such as neurons, myocytes, and certain types of glia, sodium channels are responsible for the rising phase of action potentials. These channels go through three different states called resting, active and inactive states.

Neurotoxin

Neurotoxins are toxins that are destructive to nerve tissue (causing neurotoxicity). Neurotoxins are an extensive class of exogenous chemical neurological insults that can adversely affect function in both developing and mature nervous tissue. The term can also be used to classify endogenous compounds, which, when abnormally contacted, can prove neurologically toxic. Though neurotoxins are often neurologically destructive, their ability to specifically target neural components is important in the study of nervous systems.

Tetraodontidae

Tetraodontidae is a family of primarily marine and estuarine fish of the order Tetraodontiformes. The family includes many familiar species variously called pufferfish, puffers, balloonfish, blowfish, blowers, blowies, bubblefish, globefish, swellfish, toadfish, toadies, toadle, honey toads, sugar toads, and sea squab. They are morphologically similar to the closely related porcupinefish, which have large external spines (unlike the thinner, hidden spines of the Tetraodontidae, which are only visible when the fish have puffed up).

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