ACTIONS OF THE INSECTICIDE FIPRONIL, ON DIELDRIN-SENSITIVE AND DIELDRIN-RESISTANT GABA RECEPTORS OF DROSOPHILA-MELANOGASTER

1 Blocking actions of the novel insecticide, fipronil, were examined on GABA responses recorded from Xenopus oocytes expressing either wild type (dieldrin-sensitive) or mutant (dieldrin-resistant) forms of the Drosphila melanogaster GABA-gated chloride channel homo-oligomer, RDL (the product of the resistance to dieldrin locus: Rdl). 2 In the case of the wild type receptor, fipronil blocked GABA-induced currents inducing both a shift to the right in the GABA dose-response curve and depressing the maximum amplitude of responses to GABA. The potency of fipronil was dependent on the GABA concentration but was unaffected by membrane potential. 3 Mutant RDL GABA-receptors, which have a naturally occurring amino acid substitution (A(302) --> S) in the putative ion-channel lining region, conferring resistance to dieldrin and picrotoxinin, were markedly less sensitive to fipronil than the wild-type receptors. 4 Fipronil antagonism is qualitatively similar to that produced by the structurally distinct compound, picrotoxinin. As the mutation A(302) --> S reduces the potency of both fipronil and picrotoxinin, homooligomeric RDL receptors should facilitate detailed studies of the molecular basis of convulsant/insecticide antagonist actions on GABA receptors.