ACTIONS OF PYRETHROID INSECTICIDES ON VOLTAGE-GATED CHLORIDE CHANNELSIN NEUROBLASTOMA-CELLS

Pyrethroid insecticides have the potential to act at several sites in excitable tissues in addition to their primary effect on sodium channe ls. We have assessed one such site, the voltage gated chloride channel . Following our previous demonstration of actions of deltamethrin on t he voltage-gated chloride channel in rats and in neuroblastoma cells, we examined the dose-response relationship for deltamethrin by patch c lamp analysis of voltage-gated channels in partially differentiated NI E115 cells. Open channel probability (P-O) was assessed in channels st epped from 0 to +20 mV for 10 seconds. Deltamethrin significantly decr eased P-O by 0.237 +/- 0.070 at 10(-10)M and, although construction of a dose-response relationship was rendered difficult by the very low w ater solubility of the pyrethroids, a decrease of 0.968 +/- 0.140 was reached at the highest concentration tested, 10(-4)M. A second Type II pyrethroid cypermethrin also decreased P-O by 0.430 +/- 0.09 at 5 x 1 0(-6)M, but the Type I pyrethroid cismethrin produced a decrease of on ly 0.188 +/- 0.08 at 2 x 10(-5)M. These effects were seen in 340 pS co nductance, calcium-independent channels. A sample of 9 calcium-depende nt channels with a conductance of 225 pS failed to show any response t o deltamethrin. We conclude that actions on calcium-independent voltag e-gated chloride channels are likely to contribute significantly to ty pe II pyrethroid toxicity. (C) 1997 Intox Press, Inc.