Cloning of an avermectin-sensitive glutamate-gated chloride channel from Caenorhabditis elegans.

Abstract

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.

• Authors: D F Cully, D K Vassilatis, K K Liu, P S Paress, L H Van der Ploeg, J M Schaeffer, J P Arena
• Journal: Nature (Nature) Vol. 371 Issue 6499 Pg. 707-11 (Oct 20 1994) ISSN: 0028-0836 [Print] England
• PMID: 7935817 (Publication Type: Journal Article)

Chemical References

• Chloride Channels
• DNA, Complementary
• Glutamic Acid
• Ivermectin
• avermectin

Topics

• Amino Acid Sequence
• Animals
• Base Sequence
• Caenorhabditis elegans (genetics, metabolism)
• Cell Membrane Permeability
• Cells, Cultured
• Chloride Channels (drug effects, genetics, physiology)
• Cloning, Molecular
• DNA, Complementary
• Electrophysiology
• Escherichia coli
• Glutamic Acid (physiology)
• Humans
• Ion Channel Gating
• Ivermectin (analogs & derivatives, pharmacology)
• Molecular Sequence Data
• Oocytes
• Sequence Homology, Amino Acid
• Xenopus