CLONING OF AN AVERMECTIN-SENSITIVE GLUTAMATE-GATED CHLORIDE CHANNEL FROM CAENORHABDITIS-ELEGANS

THE avermectins are a family of macrocyclic lactones used in the contr ol of nematode and arthropod parasites(1). Ivermectin (22,23-dihydroav ermectin B-1a) is widely used as an anthelmintic in veterinary medicin e and is used to treat onchocerciasis or river blindness in humans(1,2 ). Abamectin (avermectin B-1a) is a miticide and insecticide used in c rop protection(1). Avermectins interact with vertebrate and invertebra te GABA receptors(3-7) and invertebrate glutamate-gated chloride chann els(8-11). The soil nematode Caenorhabditis elegans has served as a us eful model to study the mechanism of action of avermectins(11-15). A C . elegans messenger RNA expressed in Xenopus oocytes encodes an averme ctin-sensitive glutamate-gated chloride channel(11,14). To elucidate t he structure and properties of this channel, we used Xenopus oocytes f or expression cloning of two functional complementary DNAs encoding an avermectin-sensitive glutamate-gated chloride channel. We find that t he electrophysiological and structural properties of these proteins in dicate that they are new members of the ligand-gated ion channel super family.