RECENT ADVANCES IN THE STUDY OF MECHANISM OF ACTION OF MARINE NEUROTOXINS

A variety of marine neurotoxins exert potent and specific actions on n euronal sodium channels. Tetrodotoxin and saxitoxin block the sodium c hannel selectively without any effect on other types of voltage-activa ted and transmitter-activated ion channels. They bind to a site near t he external orifice of the sodium channel on a one-to-one stoichiometr ic basis. The block is influenced by the membrane potential in a compl ex manner, and binding and penetration of calcium ions to the sodium c hannel appear to be responsible for the voltage-dependent block. Owing to the potent and specific sodium channel blocking action, tetrodotox in and saxitoxin ha ve been used extensively in various studies of ion channels. The dorsal root ganglion neurons of the rat are endowed wit h tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels. T he latter is also resistant to saxitoxin. These two types of sodium ch annels exhibit different physiological and pharmacological profiles. T etrodotoxin-resistant sodium channels are slower in time course and op en and inactivate at less negative membrane potentials than tetrodotox in-sensitive sodium channels. Lidocaine blocks tetrodotoxin-sensitive sodium channels more potently than tetrodotoxin-resistant sodium chann els. However, Pb2+ and Cd2+ block tetrodotoxin-resistant channels more strongly. The pyrethroid insecticide allethrin modifies tetrodotoxin- resistant sodium channels while affecting tetrodotoxin-sensitive sodiu m channels to a much lesser extent. The differences in pharmacological and toxicological profiles between the two types of sodium channels a re deemed critically important in understanding the mechanisms of acti on of various chemicals in animals. (C) 1994 Intox Press, Inc.