title: Actions of pyrethroid insecticides on voltage-gated chloride channels in neuroblastoma cells.
abstract: Pyrethroid insecticides have the potential to act at several sites in excitable tissues in addition to their primary effect on sodium channels. We have assessed one such site, the voltage gated chloride channel. Following our previous demonstration of actions of deltamethrin on the voltage-gated chloride channel in rats and in neuroblastoma cells, we examined the dose-response relationship for deltamethrin by patch clamp analysis of voltage-gated channels in partially differentiated NIE115 cells. Open channel probability (P0) was assessed in channels stepped from 0 to +20 mV for 10 seconds. Deltamethrin significantly decreased P0 by 0.237+/-0.070 at 10(-10) M and, although construction of a dose-response relationship was rendered difficult by the very low water 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 P0, by 0.430+/-0.09 at 5 x 10(-6) M, but the Type I pyrethroid cismethrin produced a decrease of only 0.188+/-0.08 at 2 x 10(-5) M. These effects were seen in 340 pS conductance, calcium-independent channels. A sample of 9 calcium-dependent channels with a conductance of 225 pS failed to show any response to deltamethrin. We conclude that actions on calcium-independent voltage-gated chloride channels are likely to contribute significantly to type II pyrethroid toxicity.
authors.affiliation: Medical Research Council Toxicology Unit, Leicester, United Kingdom.
authors.forename: D E
authors.initials: DE
authors.lastname: Ray
authors.forename: S
authors.initials: S
authors.lastname: Sutharsan
authors.forename: P J
authors.initials: PJ
authors.lastname: Forshaw
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007306:Insecticides / Q000633:toxicity*; D009447:Neuroblastoma / Q000188:drug therapy; D009570:Nitriles; D018408:Patch-Clamp Techniques; D011722:Pyrethrins / Q000494:pharmacology*; D051381:Rats
chemical_list: D018118:Chloride Channels; D007306:Insecticides; D009570:Nitriles; D011722:Pyrethrins; C017180:decamethrin