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PMID: 9312045 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S.

avr-15 encodes a chloride channel subunit that mediates inhibitory glutamatergic neurotransmission and ivermectin sensitivity in Caenorhabditis elegans.

The EMBO journal ·Vol. 16 ·No. 19 ·1997-10-01 ·Pages 5867-79

Dent JA, Davis MW, Avery L

Abstract

Ivermectin is a widely used anthelmintic drug whose nematocidal mechanism is incompletely understood. We have used Caenorhabditis elegans as a model system to understand ivermectin's effects. We found that the M3 neurons of the C.elegans pharynx form fast inhibitory glutamatergic neuromuscular synapses. avr-15, a gene that confers ivermectin sensitivity on worms, is necessary postsynaptically for a functional M3 synapse and for the hyperpolarizing effect of glutamate on pharyngeal muscle. avr-15 encodes two alternatively spliced channel subunits that share ligand binding and transmembrane domains and are members of the family of glutamate-gated chloride channel subunits. An avr-15-encoded subunit forms a homomeric channel that is ivermectin-sensitive and glutamate-gated. These results indicate that: (i) an ivermectin-sensitive chloride channel mediates fast inhibitory glutamatergic neuromuscular transmission; and (ii) a nematocidal property of ivermectin derives from its activity as an agonist of glutamate-gated chloride channels in essential excitable cells such as those of the pharynx.

MeSH Terms
Alternative Splicing Animals Antinematodal Agents/pharmacology Caenorhabditis elegans/drug effects,genetics,metabolism Chloride Channels/drug effects,genetics,metabolism Glutamic Acid/metabolism Iontophoresis Ivermectin/pharmacology Molecular Sequence Data Muscle Relaxation/drug effects Pharynx/metabolism Synaptic Transmission/drug effects
Chemicals
Antinematodal Agents Chloride Channels Glutamic Acid Ivermectin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Dent J A
Department of Molecular Biology and Oncology, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75235-9148, USA.
Davis M W
Avery L
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/16.19.5867
Published
1997-10-01
Pages
5867-79
Language
English
Region
England
NLM ID
8208664
PMCID
PMC1170218
Subset
IM
Grants
NIGMS NIH HHS · 5T32GM08203 · United States
Databases
GENBANK
AJ000537, AJ000538
External Links
PubMed source DOI: 10.1093/emboj/16.19.5867 PMC Full Text View journal details
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