Critically for the general argument, Takifugu rubripes puffers captured and raised in laboratory on controlled, TTX-free diets "lose toxicity over time," while cultured, TTX-free Takifugu niphobles puffers fed on TTX-containing diets saw TTX in the livers of the fishes increase to toxic levels. To the contrary, there has been a failure in a single case, that of newts ( Taricha granulosa), to detect TTX-producing bacteria in the tissues with highest toxin levels ( skin, ovaries, muscle), using PCR methods, although technical concerns about the approach have been raised. The association of bacterial species with the production of the toxin is unequivocal – Lago and coworkers state, "ndocellular symbiotic bacteria have been proposed as a possible source of eukaryotic TTX by means of an exogenous pathway," and Chau and coworkers note that the "widespread occurrence of TTX in phylogenetically distinct organisms… strongly suggests that symbiotic bacteria play a role in TTX biosynthesis" – although the correlation has been extended to most but not all metazoans in which the toxin has been identified. Vibrio species, again, in ribbon worms, phylum Nemertea.Vibrio species including Vibrio alginolyticus again, in arrow worms, phylum Chaetognatha,.Vibrio species including Vibrio alginolyticus, from the puffer fish, Takifugu vermicularis,.Vibrio alginolyticus, from the starfish species Astropecten polyacanthus,.Alteromonas, Bacillus, Pseudomonas, and Vibrio species from the Southern blue-ringed octopus, Hapalochlaena maculosa,.Aeromonas, Pseudomonas, and Vibrio species from the gastropod Nassarius conoidalis,.Aeromonas species from the puffer fish, Takifugu obscurus,.note, "there is good evidence that uptake of bacteria producing TTX is an important element of TTX toxicity in marine metazoans that present this toxin." TTX-producing bacteria include Actinomyces, Aeromonas, Alteromonas, Bacillus, Pseudomonas, and Vibrio species in the following animals, specific bacterial species have been implicated: The association of TTX with consumed, infecting, or symbiotic bacterial populations within the metazoan species from which it is isolated is relatively clear presence of TTX-producing bacteria within a metazoan's microbiome is determined by culture methods, the presence of the toxin by chemical analysis, and the association of the bacteria with TTX production by toxicity assay of media in which suspected bacteria are grown. Even though the toxin acts as a defense mechanism, some predators such as the common garter snake have developed insensitivity to TTX, which allows them to prey upon toxic newts. The toxin is variously used by metazoans as a defensive biotoxin to ward off predation, or as both a defensive and predatory venom (e.g., in octopuses, chaetognaths, and ribbon worms). Tarichatoxin was shown to be identical to TTX in 1964 by Mosher et al., and the identity of maculotoxin and TTX was reported in Science in 1978, and the synonymity of these two toxins is supported in modern reports (e.g., at Pubchem and in modern toxicology textbooks ) though historic monographs questioning this continue in reprint. the western or rough-skinned newts ( Taricha wherein it was originally termed "tarichatoxin"),.the eastern newt ( Notophthalmus viridescens).land planarians of the genus Bipalium,.species of Chaetognatha (arrow worms),.several starfish, including Astropecten species,.all octopuses and cuttlefish in small amounts, but specifically several species of the blue-ringed octopus, including Hapalochlaena maculosa (where it was called "maculotoxin"),.Moore at Duke University, using the sucrose gap voltage clamp technique. Its mechanism of action, selective blocking of the sodium channel, was shown definitively in 1964 by Toshio Narahashi and John W. This prevents the nervous system from carrying messages and thus muscles from contracting in response to nervous stimulation. 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. Tetrodotoxin is a sodium channel blocker. 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. Its name derives from Tetraodontiformes, an order that includes pufferfish, porcupinefish, ocean sunfish, and triggerfish several of these species carry the toxin. Tetrodotoxin ( TTX) is a potent neurotoxin.
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