title: Actions of the pyrethroid insecticides cismethrin and cypermethrin on house fly Vssc1 sodium channels expressed in Xenopus oocytes.
abstract: Voltage-sensitive sodium channels encoded by the Vssc1 gene of the house fly (Musca domestica) were expressed in Xenopus laevis oocytes in combination with the tipE gene product of Drosophila melanogaster and were characterized by two-electrode voltage clamp. Vssc1/tipE sodium channels expressed in oocytes were highly sensitive to tetrodotoxin; half-maximal inhibition of sodium currents by tetrodotoxin was obtained at a concentration of 2.4 nM. Cismethrin, a pyrethroid that produces Type I effects on intact nerve, slowed the inactivation of sodium currents carried by Vssc1/tipE channels during a depolarizing pulse and induced a tail current after repolarization that decayed with a first-order time constant of approximately 650 ms. The voltage dependence of activation and steady-state inactivation of cismethrin-modified channels were shifted to more negative potentials. Cypermethrin, a pyrethroid with Type II effects on intact nerve, also prolonged the inactivation of Vssc1/tipE sodium channels and induced a tail current. However, the cypermethrin-induced tail current was extremely persistent, decaying with a first-order time constant of approximately 42 s. Unlike cismethrin, the effect of cypermethrin was use dependent, requiring repeated depolarizing pulses for the full development of modified sodium currents. The divergent effects of cismethrin and cypermethrin on Vssc1/tipE sodium channels expressed in oocytes are consistent with the actions of these and related compounds on sodium channels in invertebrate and vertebrate nerve preparations and provide insight into the mechanisms underlying the production of Type I and II effects on neuronal excitability.
authors.affiliation: Department of Entomology, New York State Agricultural Experiment Station, Cornell University, Geneva 14456, USA.
authors.forename: T J
authors.initials: TJ
authors.lastname: Smith
authors.forename: P J
authors.initials: PJ
authors.lastname: Ingles
authors.forename: D M
authors.initials: DM
authors.lastname: Soderlund
mesh_terms: D000818:Animals; D004331:Drosophila melanogaster; D005260:Female; D006793:Houseflies; D007306:Insecticides / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009865:Oocytes / Q000187:drug effects / Q000502:physiology*; D011722:Pyrethrins / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000096:biosynthesis; D015222:Sodium Channels / Q000096:biosynthesis / Q000187:drug effects / Q000502:physiology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014982:Xenopus laevis
chemical_list: D007306:Insecticides; D011722:Pyrethrins; D011994:Recombinant Proteins; D015222:Sodium Channels; C017160:cypermethrin; C017498:cismethrin; D013779:Tetrodotoxin