title: Interactions of pyrethroids and octylguanidine with sodium channels of squid giant axons.
abstract: Kinetics of pyrethroid-modified sodium channels and the interaction of N-octylguanidine with the modified channels have been studied with internally perfused and voltage-clamped squid giant axons. The pyrethroids used were 1R-cis-phenothrin; 1R-cis-permethrin; 1R-cis-cyphenothrin; and 1R-cis-deltamethrin. Modification of sodium channels by pyrethroids resulted in marked slowing of opening and closing kinetics. The rate at which sodium channels arrived at the open pyrethroid-modified state during a depolarizing step was independent of the concentration of pyrethroids applied. The time of exposure to pyrethroids required for the pyrethroid-induced sodium tail current following a step depolarization to reach a steady-state amplitude was independent of the frequency of short (5 ms) depolarizing pulses, and in the pronase-treated axons was independent of the membrane potential (0 mV or -90 mV). We conclude that sodium channels are modified by pyrethroids primarily in the closed resting state. A small fraction of sodium channels is modified in the open state. The dose-response curve for N-octylguanidine block of sodium channels was not shifted by pyrethroids. The rate at which the pyrethroid-modified sodium channels were blocked by octylguanidine during a depolarizing step depended neither on the concentration of pyrethroids nor on the depolarizing potential, but depended on the concentration of octylguanidine. The time course of the pyrethroid-induced slow sodium tail current was not altered by octylguanidine. We conclude that the actions of pyrethroids and N-octylguanidine on sodium channels are independent of each other.
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D049832:Decapodiformes; D006146:Guanidines / Q000494:pharmacology*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D011722:Pyrethrins / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*
chemical_list: D006146:Guanidines; D007473:Ion Channels; D011722:Pyrethrins; C015403:octylguanidine; D012964:Sodium