Potent Actions of the Pyrethroid Insecticides Cismethrin and Cypermethrin on Rat Tetrodotoxin-Resistant Peripheral Nerve (SNS/PN3) Sodium Channels Expressed in Xenopus Oocytes

Abstract

Abstract The rat peripheral nerve tetrodotoxin (TTX)-resistant voltage-sensitive sodium channel (designated SNS/PN3) was expressed in Xenopus laevis oocytes, and the responses of the expressed channels to two pyrethroid insecticides, cismethrin and cypermethrin, were assessed by recording macroscopic sodium currents under voltage clamp conditions. Each pyrethroid produced two distinct modifications of sodium currents carried by SNS/PN3 channels: a sustained, slowly inactivating current evident during a depolarizing pulse and a prominent tail current following repolarization. In addition, high concentrations of cismethrin produced a reduction of the amplitude of the peak transient sodium current. Cismethrin-induced tail currents decayed with a first-order decay constant (τ) of 14.7 ms, whereas cypermethrin-induced tail currents were much more persistent (τ = 558 ms). Modified currents were obtained in the presence of nanomolar concentrations of each compound, and the amplitude of the modified currents exhibited a strong concentration dependence. High concentrations of cismethrin and cypermethrin shifted the voltage dependence of activation of SNS/PN3 sodium channels by ∼5 mV in the direction of hyperpolarization and the voltage dependence of steady-state inactivation by ∼8–10 mV in the direction of depolarization. The high sensitivity of the SNS/PN3 sodium channel to pyrethroids is consistent with the identification of this channel isoform as the principal carrier of the TTX-resistant, pyrethroid-sensitive sodium current of dorsal root ganglion neurons.