IDENTIFICATION OF A DROSOPHILA-MELANOGASTER GLUTAMATE-GATED CHLORIDE CHANNEL SENSITIVE TO THE ANTIPARASITIC AGENT AVERMECTIN

Glutamate-gated chloride channels, members of the ligand-gated ion cha nnel superfamily, have been shown in nematodes and in insects to be a target of the antiparasitic agent avermectin. Two subunits of the Caen orhabditis elegans glutamate-gated chloride channel have been cloned: GluCl-alpha and GluCl-beta. We report the cloning of a Drosophila mela nogaster glutamate-gated chloride channel, DrosGluCl-alpha, which shar es 48% amino acid and 60% nucleotide identity with the C. elegans GluC l channels. Expression of DrosGluCl-alpha in Xenopus oocytes produces a homomeric chloride channel that is gated by both glutamate and averm ectin. The DrosGluCl-alpha channel has several unique characteristics not observed in C. elegans GluCl: dual gating by avermectin and glutam ate, a rapidly desensitizing glutamate response, and a lack of potenti ation of the glutamate response by avermectin. The pharmacological dat a support the hypothesis that the DrosGluCl-alpha channel represents t he arthropod H-receptor and an important target for the avermectin cla ss of insecticides.