Genetically encoded calcium indicators as probes to assess the role of calcium channels in disease and for high-throughput drug discovery

The calcium ion (Ca) is an important signaling molecule implicated in many cellular processes, and the remodeling of Ca homeostasis is a feature of a variety of pathologies. Typical methods to assess Ca signaling in cells often employ small molecule fluorescent dyes, which are sometimes poorly suited to certain applications such as assessment of cellular processes, which occur over long periods (hours or days) or in vivo experiments. Genetically encoded calcium indicators are a set of tools available for the measurement of Ca changes in the cytosol and subcellular compartments, which circumvent some of the inherent limitations of small molecule Ca probes. Recent advances in genetically encoded calcium sensors have greatly increased their ability to provide reliable monitoring of Ca changes in mammalian cells. New genetically encoded calcium indicators have diverse options in terms of targeting, Ca affinity and fluorescence spectra, and this will further enhance their potential use in high-throughput drug discovery and other assays. This review will outline the methods available for Ca measurement in cells, with a focus on genetically encoded calcium sensors. How these sensors will improve our understanding of the deregulation of Ca handling in disease and their application to high-throughput identification of drug leads will also be discussed