Flux assays in high throughput screening of ion channels in drug discovery.
Ion channels have been identified as therapeutic targets in various disorders, such as cardiovascular disease, neurological disease, and cystic fibrosis. Flux assays to detect functional ionic flux through ion channels are becoming increasingly popular as tools for screening compounds. In an optimized flux assay, modulation of ion channel activity may produce readily detectable changes in radiolabeled or nonradiolabeled ionic flux. Technologies based on flux assays are currently available in a fully automated high throughput format for efficient screening. This application offers sensitive, precise, and reproducible measurements giving accurate drug rank orders matching those of patch clamp data. Conveniently, the flux assay is amenable to adaptation for different ion channels, such as potassium, sodium, calcium, and chloride channels, by using suitable tracer ions. The nonradiolabeled rubidium-based flux assay coupled with the ion channel reader (ICR) technology has become very successful in ion channel activity analysis and is emerging as a popular technique in modern drug discovery.
Gill
Sikander
S
Aurora Biomed Inc, Vancouver, BC, Canada. gill@aurorabiomed.com
Gill
Raj
R
Lee
Soo Sen
SS
Hesketh
J Christian
JC
Fedida
David
D
Rezazadeh
Saman
S
Stankovich
Larisa
L
Liang
Dong
D
D000818:Animals; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D007473:Ion Channels / Q000032:analysis / Q000187:drug effects* / Q000502:physiology*; D017136:Ion Transport / Q000187:drug effects* / Q000502:physiology*; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000295:instrumentation / Q000379:methods*; D011869:Radioligand Assay / Q000295:instrumentation / Q000379:methods*; D013050:Spectrometry, Fluorescence / Q000295:instrumentation / Q000379:methods*; D013673:Technology Assessment, Biomedical
D007473:Ion Channels