Sodium channels toxins

Tetrodotoxin, saxitoxin, ciguatoxin, and batrachotoxin are sodium-channel toxins found in various fish, frogs, or diflageliates. 

The pyrethrins and pyrethrolds (permethrin) are nerve membrane sodium channel toxins that do not affect potassium channels. The compounds bind to specific sodium channel proteins and slow the rate of Inactivation of the sodium current elicited by membrane depolarization and, as a result, prolong the open time of the sodium channel. At low ooncentratlons, the pyrethrolds produce repetitive action potentials and neuron firing at high concentrations, the nerve membrane is depolarized completely and excitation blocked. 

Manger, R.L. et al., Detection of sodium channel toxins directed cytotoxicity assays of purified cigua-toxins, brevetoxins, saxitoxins, and seafood extracts, J AOAC Int 78, 521, 1995. 

Manger, R. L., Leja, L. S., Lee, S. Y. et al.. Detection of sodium channel toxins directed cytotoxicity assays of purified ciguatoxins, brevetoxins, saxitoxins, and seafood extracts, J. AOAC Int. 78, 521, 1995 Dechraoui, M. Y, Naar, J., PauUlac, S. et al., Ciguatoxins and brevetoxins, neurotoxic polyether compounds active on sodium chaimels, Toxicon 37, 125, 1999. 

Bidard JN, Vijverberg HPM, Frelin C, Chungue E, Legrand AM (1984) Ciguatoxin is a novel type of sodium channel toxin. J Biol Chem 259(13) 8353-8357. 

Kelso, G.J. and Blumenihal, K.M. (1998) Identification and characterization o f novel sodium channel toxins from ftie sea anemone Anthpleura xanthogrammica. Toxicon. 36, 41-51. 

Lin, X., Ishida, M Nagashima, Y, and Shiorai, K. (1996) Apolypeptide toxin in the sea anemone Actinia equina homologous with other sea anemone sodium channel toxins isolation and amino add sequence. Toxicon, 34, 57-65. 

In order to further characterize the TxVIA receptor, we tested the ability of several sodium channel neurotoxins to compete with I-labeled TxVIA binding. As can be seen in Fig. 2 A, sodium channel toxins that bind to receptor sites 1 (tetrodotoxin), 3 (sea anemone toxin II), 4 (P-scorpion toxin), and 5 (brevetoxin-PbTx-1) on sodium channels do not inhibit binding of TxVIA. On the other hand, both CsTx and GPT compete with TxVIA and completely inhibit its binding in both rat and Helix membranes. Interestingly the lipid-soluble channel activator veratridine, which binds to receptor site 2 on the sodium channel, also reduces specific binding of TxVIA. The isotoxin TxVIB, and also peptide fractions from additional Conus venoms, are able to completely inhibit TxVIA binding in both Helix and rat membranes (Fig. 2A and data not shown). 

TxVIA Represents a New Category of Sodium Channel Toxins... 

Sensitive to toxins, in this case means that the assay presents no false negative results. Primary hepatocytes can elucidate hepatotoxins, and mouse neuroblastoma cells can elucidate sodium channel-blocking neurotoxins therefore these assays can be used to screen for the appropriate toxins. 

Turning now to chemical attack, many predators immobilize their prey by injecting toxins, often neurotoxins, into them. Examples include venomous snakes, spiders, and scorpions. Some spider toxins (Quick and Usherwood 1990 Figure 1.3) are neurotoxic through antagonistic action upon glutamate receptors. The venom of some scorpions contains polypeptide neurotoxins that bind to the sodium channel. 

Differences in the equilibrium dissociation constant, K, for the binding of the various saxitoxins to the sodium channel binding site largely determine the differences in the potencies of the toxins in whole animal assays and in tissue preparations. 

Tetrodotoxin (TTX) and saxitoxin (STX) are potent sodium channel blockers that are found in phylogenetically diverse species of marine life. The wide distribution of TTX and STX has resulted in speculation that bacteria are the source of these toxins. Recently, investigators have reported isolation of marine bacteria, including Vibrio Alteromonas, Plesiomonas, and Pseudomonas species, that produce TTX and STX. This chapter details the methods and results of research to define bacterial sources of TTX and STX. 

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