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 parasites1. Ivermectin (22,23-dihydroavermectin Bla) is widely used as an anthelmintic in veterinary medicine and is used to treat onchocerciasis or river blindness in humans1,2. Abamectin (avermectin B1a) is a miticide and insecticide used in crop protection1. Avermectins interact with vertebrate and invertebrate GABA receptors3–7 and invertebrate glutamate-gated chloride channels8–11. The soil nematode Caenorhabditis elegans has served as a useful model to study the mechanism of action of avermectins11–15. A C. elegans messenger RNA expressed in Xenopus oocytes encodes an avermectin-sensitive glutamate-gated chloride channel11,14. 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.