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

THE avermectins are a family of macrocyclic lactones used in the control of nematode and arthropod parasites(1). Ivermectin (22,23-dihydroavermectin B-1a) is widely used as an anthelmintic in veterinary medicine and is used to treat onchocerciasis or river blindness in humans(1,2). Abamectin (avermectin B-1a) is a miticide and insecticide used in crop protection(1). Avermectins interact with vertebrate and invertebrate GABA receptors(3-7) and invertebrate glutamate-gated chloride channels(8-11). The soil nematode Caenorhabditis elegans has served as a useful model to study the mechanism of action of avermectins(11-15). A C. elegans messenger RNA expressed in Xenopus oocytes encodes an avermectin-sensitive glutamate-gated chloride channel(11,14). To elucidate the structure and properties of this channel, we used Xenopus oocytes for expression cloning of two functional complementary DNAs encoding an avermectin-sensitive glutamate-gated chloride channel. We find that the electrophysiological and structural properties of these proteins indicate that they are new members of the ligand-gated ion channel superfamily.