Flux Assays in High Throughput Screening of Ion Channels in Drug Discovery
- 1 October 2003
- journal article
- research article
- Published by Mary Ann Liebert Inc in ASSAY and Drug Development Technologies
- Vol. 1 (5), 709-717
- https://doi.org/10.1089/154065803770381066
Abstract
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.Keywords
This publication has 57 references indexed in Scilit:
- Meeting the challenges inscreeningDrug Discovery Today, 2002
- A “Minimal” Sodium Channel Construct Consisting of Ligated S5-P-S6 Segments Forms a Toxin-activatable IonophorePublished by Elsevier ,2002
- A High-Throughput HERG Potassium Channel Function Assay: An Old Assay with a New LookDrug Development and Industrial Pharmacy, 2002
- G protein modulation of recombinant P/Q‐type calcium channels by regulators of G protein signalling proteinsThe Journal of Physiology, 2000
- Zn2+ current is mediated by voltage‐gated Ca2+ channels and enhanced by extracellular acidity in mouse cortical neuronesThe Journal of Physiology, 2000
- Channelopathies: ion channel defects linked to heritable clinical disordersJournal of Medical Genetics, 2000
- A Simple Statistical Parameter for Use in Evaluation and Validation of High Throughput Screening AssaysSLAS Discovery, 1999
- Potassium ion channels and human disease: phenotypes to drug targets?Current Opinion in Biotechnology, 1998
- Miniaturization technologies in HTS: how fast, how small, how soon?Drug Discovery Today, 1998
- Blockade of HERG channels expressed in Xenopus oocytes by the histamine receptor antagonists terfenadine and astemizoleFEBS Letters, 1996