Recent Advances in Ion Channel Screening Technologies

Abstract

Ion channels play a vital role in basic physiological functions such as generation of electrical activity in nerves and muscle, control of cardiac excitability, intracellular signaling, hormone secretion, cell proliferation, cell volume regulation, and many other biological processes. Because of their prevalence and the critical role they play in virtually all tissue types and organs, ion channels are also involved in a number of pathophysiological conditions. The recognized importance of ion channels in health and disease, combined with the potential to develop new drugs targeting ion channels in a broad range of diseases, has fueled the need to develop more suitable screening technologies accounting for their complex structure and function. Ion channels have been neglected as drug discovery targets because of the inability to study large number of compounds or validate large numbers of unknown or mutant ion channel genes using traditional ion channel screening technologies. Therefore, several efforts were undertaken to automate and improve the throughput of electrophysiological methods. In this chapter, we will review a number of the more standard ion channel screening technologies currently used, including: (1) radioligand binding assays, (2) fluorescent assays using membrane potential dyes, and (3) ion flux assays, and emphasize some of the advantages and shortcomings of these different approaches. We will then discuss automated patch clamp technologies that aim to automate and dramatically increase the throughput of the standard voltage clamp method, and offer a true archetype shift in ion channel drug discovery.