A thallium-sensitive, fluorescence-based assay for detecting and characterizing potassium channel modulators in mammalian cells.
Potassium channels have been identified as targets for a large number of therapeutic indications. The ability to use a high-throughput functional assay for the detection and characterization of small-molecule modulators of potassium channels is very desirable. However, present techniques capable of screening very large chemical libraries are limited in terms of data quality, temporal resolution, ease of use, and requirements for specialized instrumentation. To address these issues, the authors have developed a fluorescence-based thallium flux assay. This assay is capable of detecting modulators of both voltage and ligand-gated potassium channels expressed in mammalian cells. The thallium flux assay can use instruments standard to most high-throughput screening laboratories, and using such equipment has been successfully employed to screen large chemical libraries consisting of hundreds of thousands of compounds.
Weaver
C David
CD
Vanderbilt Institute of Chemical Biology and Department of Pharmacology, 812 Robinson Research Building, Nashville, TN 37232-6600, USA. david.weaver@vanderbilt.edu
Harden
David
D
Dworetzky
Steven I
SI
Robertson
Barbara
B
Knox
Ronald J
RJ
D001681:Biological Assay; D002460:Cell Line; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D018408:Patch-Clamp Techniques; D010539:Permeability; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*; D013793:Thallium / Q000737:chemistry*
D005456:Fluorescent Dyes; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D013793:Thallium