Voltage-sensitive Na+ channel

FIGURE 17.26 The o i-subuiiit of the t-tubule Ca" chainiel/DHP receptor contains six peptide segments that may associate to form the Ca" channel. This Ca" channel polypeptide is homologous with the voltage-sensitive Na channel of neuronal tissue. 

Saxitoxin (STX) is a toxin which is found in marine microorganisms. It is most likely synthesized by bacteria which live in symbiosis with dinoflagellates, a component of phytoplankton. Through the marine food chain, it can lead to poisoning of humans. The mechanism of toxicity of saxitoxin is vety similar to that of tetrodotoxin. Saxitoxin binds from the outside of the membrane to various forms of voltage-sensitive Na+channels and blocks the channel in an activation state-independent manner. 

Tetrodotoxin (TTX) is a toxin derived from bacteria which is concentrated in the gonads and liver of certain pufferfishes (fugu). Similar to saxitoxin, tetrodotoxin is a very potent blocker of most voltage-sensitive Na+ channels. 

Another potentially paralytic conotoxin was recently described this was a peptide purified from Conus geographus venom, which like / -conotoxin appeared to target to voltage-sensitive Na channels. However, the structure of "conotoxin GS" [nomenclature of Yanagawa et al. (J7)] was less homologous to / -conotoxins than to the w-conotoxins, which are Ca channel blockers. The same peptide was purified and characterized using a different assay, the induction of highly aberrant behavior upon ic injection of mice (L. J. Cruz, unpublished data). 

Carbamazepine Tegretol, Epitol Tablet 200 mg 200-1,800 m day in 2-4 divided doses. Use alone or in combination with other medications Blocks voltage-sensitive Na+ channels Stimulates the release of antidiuretic hormone and decreases Na+... 

Many fish species, over 700 species worldwide, are either directly toxic or upon ingestion are poisonous to humans. A classic example is the toxin produced by the puffer fishes (Sphaeroides spp.) called tetrodotoxin (TTX). Tetrodotoxin is concentrated in the gonads, liver, intestine, and skin, and poisonings occurs most frequently in Japan and other Asian countries where the flesh, considered a delicacy, is eaten as fugu. Death occurs within 5 to 30 minutes and the fatality rate is about 60%. TTX is an inhibitor of the voltage-sensitive Na channel (like saxitoxin) it may also be found in some salamanders and may be bacterial in origin. 

Fig. 3.27. Photoaffinity reagents made by attaching photoactivatabie groups to readily available ligands, a Cardiac glycoside derivative for reaction with Na,K-ATPase. The reactive secondary hydroxyl of cymarin was reacted with ethyldiazomalonyl chloride (Ruoho and Kyte, 1974, 1977). b Tetrodotoxin derivative for reaction with the voltage-sensitive Na-channel. Tetrodotoxin was oxidised with periodate to form a ketone which was reacted with an azidoarylhydrazide (Chicheportiche et al., 1979).

Salty tastants act directly on Na+ channels in the PM of cells on the tongue surface. Direct passage of Na+ through these channels causes depolarization and thence signalling to the CNS. Much (but not all) salt taste perception is inhibited by the voltage-sensitive Na+ channel inhibitor amiloride (see Chapter 4) and evidently some salt perception also occurs via amiloride-insensitive channels. 

Blocks voltage-sensitive Na channels Stimulates the release of antidiuretic hormone and decreases Na serum concentrations Blocks Ca influx through the NMDA glutamate receptor and decreases Ca serum concentrations Modulates presynaptic asparate and glutamate release... 

James WM, Agnew WS (1987) Mnltiple oligosaccharide chains in the voltage-sensitive Na channel from electrophoms electricns evidence for alpha-2,8-linked polysialic acid. Biochem Biophys Res Commnn 148 817-826... 

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