Advances in functional assays for high-throughput screening of ion channels targets.

IMPORTANCE OF THE FIELD: Ion channels are important targets for many disease areas but are challenging to screen due to lack of technologies enabling robust high-throughput assays, particularly for state-dependent interactions. AREAS COVERED IN THIS REVIEW: Current assay technologies used to measure ion channel function are reviewed and assessed for use in high-throughput screening (HTS). An iterative approach to screening is evaluated as an alternative to full collection screening in order to take advantage of low-throughput, high cost assays that yield high quality data. WHAT THE READER WILL GAIN: The reader will gain an understanding of the advantages and disadvantages of various assay techniques used to screen ion channels and their suitability for use in HTS. TAKE HOME MESSAGE: Assays that directly measure ion channel function are prone to less artifact and higher hit confirmation in screening than those using an indirect measure but they are usually lower throughput. However, an iterative approach to screening can make the relatively lower throughput techniques amenable for use in interrogating large collections of compounds.