Tetrodotoxins sodium channel blocking

Action potential propagation Local anesthetics, tetrodotoxin,1 saxitoxin2 Nerve axons Block sodium channels block conduction... 

Figure 11. Comparative potencies of several saxitoxins and tetrodotoxin in the mouse bioassay, displacement of radiolabelled saxitoxin from rabbit brain, and block of single batrachotoxin-treated rat sarcolemmal sodium channels incorporated into planar lipid bilayers. The horizontal axis is the log of the potency relative to saxitoxin. Compound numbering corresponds to that in Figure 1. Data from Ref. 10, 94, 95.

The tetrodotoxins (TTXs) and saxitoxins (STXs) have in common the ability to block sodium channels of excitable membranes (1—5), Saxitoxin and tetrodotoxin are some of the most potent non-proteinaceous neurotoxins known and are responsible for significant human morbidity and mortality (6, 7). Although for many years the biosynthetic origin(s) of TTXs and STXs has not been identified, recent evidence indicates that bacteria may be a source. 

Terlau, H., Heinemann, S. H., Stiihmer, W. et al. Mapping the site of block by tetrodotoxin and saxitoxin of sodium channel II. FEBS Lett. 293,93-96,1991. 

There appear to be at least two kinds of sodium channels, the common ones which are blocked by tetrodotoxin and alternate ones which are not affected by tetrodotoxin (57,58). It seems reasonable that species with a preponderance of this alternate type of sodium channel might evolve as the predominate form in response to the presence of tetrodotoxin. It is completely reasonable that in the presence of tetrodotoxin, species would be selected in which the nerve... 

Several isoforms of the sodium channel have been identified, and they have differing sensitivities to channel-blocking drugs such as tetrodotoxin. There is also evidence that some sodium channels are much more sensitive to local anesthetics than the classic channels associated with axonal transmission. 

The 1960s saw the discovery of a number of specific channel-blocking agents. Tetrodotoxin, for example, from the fugu puffer fish, specifically blocks voltagegated sodium channels. This provided very convincing confirmation that the sodium and potassium channels of nerve axons really are separate from each other. It also allowed potassium channels in nerves to be studied on their own, permitted estimates of channel densities in the membrane to be made, and ultimately proved crucial in the biochemical isolation of sodium channels. 

Tetrodotoxin (TTX, 1) is one of the best known marine toxins and exhibits potent neurotoxicity by specifically blocking the sodium channels of excitable cell membranes. The etiology of TTX has been an interesting topic because of the wide distribution of the toxin among genetically... 

Chiriquitoxin is nearly as toxic as tetrodotoxin, having an LD50 in mice of about 0.3 fig. Pharmacologically, chiriquitoxin, like tetrodotoxin, blocks voltage-dependent sodium channels, but in addition it apparently also blocks potassium channels (211,213). The effects of chiriquitoxin on potassium currents were prevented by tetrodotoxin. 

Chemical Abstracts Service Registry Number CAS 4368-28-9. Tetrodotoxin, a neurotoxin produced by several species of starfish, crabs, salt-water fish, octopi, newts, and salamanders, blocks sodium channels within neurons. In a terrorist scenario, tetrodotoxin could be inhaled as an aerosol or ingested in contaminated food or water. Mortality may reach 50%. 

Different ion channels maintain the stability of excitable membranes that are necessary for normal functioning of the body. Saxitoxin, tetrodotoxin, and DDT all cause toxicity by blocking the sodium channel in excitable membranes. On the other hand, organic solvents cause toxicity by changing the membrane fluidity of the neurones in the central nervous system. 

Tetrodotoxin is believed to be synthesized by a bacterial or dinoflagellate species. Tetrodotoxin blocks axonal transmission by lowering the conductance of sodium at nodes of Ranvier. It is a selective sodium channel blocker that can block nerve and muscle conduction action potentials are blocked while resting membrane potentials and resting membrane resistance are not affected. Tetrodotoxin does not... 

Basic polypeptide toxin from rattlesnake Crotalus terrificus. Activates sodium channels in muscle depolarization and contracture, blocked by tetrodotoxin. See also crotoxin. 

LSnnendonker U (1989) Use-dependent block of sodium channels in frog myelinated nerve by tetrodotoxin and saxitoxin at negative holding potentials. Biochim Biophys Acta 985 153-160... 

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