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- Title
A High-Throughput Assay for Modulators of Ligand-Gated Chloride Channels.
- Authors
Michel Hamelin; Xin Meng; Michael Cuddy; Keith Korsun; John Ondeyka; Peter B. Simpson; Doris F. Cully; Birgit T. Priest
- Abstract
Invertebrate glutamate-gated chloride channels (GluCls) are important targets foranthelmintics and insecticides such as ivermectin. To facilitate screening for novel GluCl modulators,the Caenorhabditis elegans GluCl α2β channel was chosen as a surrogate for parasite channels not yet cloned, and an inducible stable human embryonic kidney cell line was generated. Functionalexpression of the α2 and β subunits was confirmed by whole-cell voltage clamp assays. Using thiscell line, a high-throughput assay was developed that detects membrane potential changes associatedwith the activation of GluCls. In this assay, membrane depolarization was quantified via changes influorescence resonance energy transfer between two membrane-associated dyes. Robust andreproducible signals were detected in response to addition of glutamate or ivermectin. This assay wasused for the screening of over 180,000 samples from natural and synthetic sources.
- Publication
Assay & Drug Development Technologies, 2005, Vol 3, Issue 1, p59
- ISSN
1540-658X
- Publication type
Article