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. Ivermectin (22,23-dihydroavermectin B1a) is widely used as an anthelmintic in veterinary medicine and is used to treat onchocerciasis or river blindness in humans. Abamectin (avermectin B1a) is a miticide and insecticide used in crop protection. Avermectins interact with vertebrate and invertebrate GABA receptors and invertebrate glutamate-gated chloride channels. The soil nematode Caenorhabditis elegans has served as a useful model to study the mechanism of action of avermectins. A C. elegans messenger RNA expressed in Xenopus oocytes encodes an avermectin-sensitive glutamate-gated chloride channel. 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.
Cully
D F
DF
Department of Cellular Biochemistry and Physiology, Merck Research Laboratories, Rahway, New Jersey 07065-0900.
Vassilatis
D K
DK
Liu
K K
KK
Paress
P S
PS
Van der Ploeg
L H
LH
Schaeffer
J M
JM
Arena
J P
JP
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000378:metabolism; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D018118:Chloride Channels / Q000187:drug effects / Q000235:genetics* / Q000502:physiology; D003001:Cloning, Molecular; D018076:DNA, Complementary; D004594:Electrophysiology; D004926:Escherichia coli; D018698:Glutamic Acid / Q000502:physiology; D006801:Humans; D015640:Ion Channel Gating; D007559:Ivermectin / Q000031:analogs & derivatives* / Q000494:pharmacology; D008969:Molecular Sequence Data; D009865:Oocytes; D017386:Sequence Homology, Amino Acid; D014981:Xenopus
D018118:Chloride Channels; D018076:DNA, Complementary; D018698:Glutamic Acid; D007559:Ivermectin; C019264:avermectin