Modification of nerve membrane sodium channels by the insecticide pyrethroids.
1. The synthetic pyrethroids exert potent and selective actions on nerve membrane sodium channels. (+)-trans tetramethrin and (+)-trans allethrin cause repetitive discharges to be produced in the isolated crayfish and squid giant axons in response to a single stimulus as a result of an increase in depolarizing after-potential. 2. The latter effect is due to slowing of the sodium channel kinetics which causes a prolonged sodium current following the normal peak sodium current. 3. A kinetic model is proposed to account for the action of the pyrethroids in which the pyrethroid molecule binds to the sodium channels at both closed and open states to produce a modified open state. 4. (-)-trans and (-)-cis isomers of tetramethrin are ineffective in causing the effects, but prevent the active (+)-trans and (+)-cis isomers from exerting the effects. This stereospecificity provides us with an excellent opportunity for the study of binding sites of pyrethroids and other sodium channel modulators.
D000200:Action Potentials / Q000187:drug effects; D000487:Allethrins / Q000494:pharmacology; D000818:Animals; D003400:Astacoidea; D001369:Axons / Q000187:drug effects*; D049832:Decapodiformes; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects*; D007700:Kinetics; D011722:Pyrethrins / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D013237:Stereoisomerism
D000487:Allethrins; D007473:Ion Channels; D011722:Pyrethrins; D012964:Sodium; C009424:tetramethrin