Use of planar array electrophysiology for the development of robust ion channel cell lines

Combinatorial Chemistry & High Throughput Screening
Jeffrey J ClareAndrew J Powell

Abstract

The tractability of ion channels as drug targets has been significantly improved by the advent of planar array electrophysiology platforms which have dramatically increased the capacity for electrophysiological profiling of lead series compounds. However, the data quality and through-put obtained with these platforms is critically dependent on the robustness of the expression reagent being used. The generation of high quality, recombinant cell lines is therefore a key step in the early phase of ion channel drug discovery and this can present significant challenges due to the diversity and organisational complexity of many channel types. This article focuses on several complex and difficult to express ion channels and illustrates how improved stable cell lines can be obtained by integration of planar array electrophysiology systems into the cell line generation process per se. By embedding this approach at multiple stages (e.g., during development of the expression strategy, during screening and validation of clonal lines, and during characterisation of the final cell line), the cycle time and success rate in obtaining robust expression of complex multi-subunit channels can be significantly improved. We also review how recent ad...Continue Reading

Citations

May 12, 2012·Assay and Drug Development Technologies·C Ian SpencerCristian Ionescu-Zanetti
Mar 24, 2011·Future Medicinal Chemistry·Georg C TerstappenRavikumar Peri
Dec 17, 2009·Expert Opinion on Investigational Drugs·Jeffrey J Clare
Oct 4, 2014·Journal of Biomolecular Screening·Mao Xiang ChenDerek Trezise

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