Reciprocal Relationship between Ca2+ Signaling and Ca2+-Gated Ion Channels as a Potential Target for Drug Discovery.

Abstract

Cellular Ca2+ signaling functions as one of the most common second messengers of various signal transduction pathways in cells and mediates a number of physiological roles in a cell-type dependent manner. Ca2+ signaling also regulates more general and fundamental cellular activities, including cell proliferation and apoptosis. Among ion channels, Ca2+-permeable channels in the plasma membrane as well as endo- and sarcoplasmic reticulum membranes play important roles in Ca2+ signaling by directly contributing to the influx of Ca2+ from extracellular spaces or its release from storage sites, respectively. Furthermore, Ca2+-gated ion channels in the plasma membrane often crosstalk reciprocally with Ca2+ signals and are central to the regulation of cellular functions. This review focuses on the physiological and pharmacological impact of i) Ca2+-gated ion channels as an apparatus for the conversion of cellular Ca2+ signals to intercellularly propagative electrical signals and ii) the opposite feedback regulation of Ca2+ signaling by Ca2+-gated ion channel activities in excitable and non-excitable cells.