Ion Channel Screening

Author(s): John Dunlop, Mark Bowlby, Ravikumar Peri, Gregory Tawa, James LaRocque, Veronica Soloveva, John Morin

Journal Name: Combinatorial Chemistry & High Throughput Screening
Accelerated Technologies for Biotechnology, Bioassays, Medicinal Chemistry and Natural Products Research

Volume 11 , Issue 7 , 2008

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Abstract:

Ion channels are attractive targets for drug discovery with recent estimates indicating that voltage and ligandgated channels account for the third and fourth largest gene families represented in company portfolios after the G protein coupled and nuclear hormone receptor families. A historical limitation on ion channel targeted drug discovery in the form of the extremely low throughput nature of the gold standard assay for assessing functional activity, patch clamp electrophysiology in mammalian cells, has been overcome by the implementation of multi-well plate format cell-based screening strategies for ion channels. These have taken advantage of various approaches to monitor ion flux or membrane potential using radioactive, non-radioactive, spectroscopic and fluorescence measurements and have significantly impacted both high-throughput screening and lead optimization efforts. In addition, major advances have been made in the development of automated electrophysiological platforms to increase capacity for cell-based screening using formats aimed at recapitulating the gold standard assay. This review addresses the options available for cell-based screening of ion channels with examples of their utility and presents case studies on the successful implementation of high-throughput screening campaigns for a ligand-gated ion channel using a fluorescent calcium indicator, and a voltage-gated ion channel using a fluorescent membrane potential sensitive dye.

Keywords: drug discovery, Ion Channel Screening, mammalian cells, electrophysiological measures, ligandgated channels, fluorescent calcium indicator

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Article Details

VOLUME: 11
ISSUE: 7
Year: 2008
Page: [514 - 522]
Pages: 9
DOI: 10.2174/138620708785204117
Price: $65

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