ACTIONS OF THE PYRETHROID INSECTICIDES CISMETHRIN AND CYPERMETHRIN ONHOUSE-FLY VSSC1 SODIUM-CHANNELS EXPRESSED IN XENOPUS OOCYTES

Voltage-sensitive sodium channels encoded by the Vssc1 gene of the hou se By (Musca domestica) were expressed in Xenopus laevis oocytes in co mbination with the tipE gene product of Drosophila melanogaster and we re characterized by two-electrode voltage clamp, Vssc1/tipE sodium cha nnels 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 Typ e I effects on intact nerve, slowed the inactivation of sodium current s carried by Vssc1/tipE channels during a depolarizing pulse and induc ed a tail current after repolarization that decayed with a first-order time constant of approximately 650 ms, The voltage dependence of acti vation and steady-state inactivation of cis-methrin-modified channels were shifted to more negative potentials. Cypermethrin, a pyrethroid w ith Type IT effects on intact nerve, also prolonged the inactivation o f Vssc1/tipE sodium channels and induced a tail current. However, the cypermethrin-induced tail current was extremely persistent, decaying w ith a first-order time constant of approximately 42 s, Unlike cismethr in, the effect of cypermethrin was use dependent, requiring repeated d epolarizing pulses for the full development of modified sodium current s. The divergent effects of cismethrin and cypermethrin on Vssc1/tipE sodium channels expressed in oocytes are consistent with the actions o f these and related compounds on sodium channels in invertebrate and v ertebrate nerve preparations and provide insight into the mechanisms u nderlying the production of Type I and II effects on neuronal excitabi lity, Arch. Insect Biochem, Physiol, 38:126-136, 1998, (C) 1998 Wiley- Liss, Inc.