The Signaling Function of Calcium and Its Regulation

Abstract

In the course of evolution Ca has become a signaling agent of universal significance, which controls a large number of cellular functions: prominent among them are the synthesis and release of hormones, muscle and non-muscle motility, and a multiplicity of membrane-linked processes (see Carafoli, 1987, for a recent comprehensive review). It is self evident that the signaling function of Ca demands its maintenance within cells at a very low free concentration, and mechanisms to efficiently modulate it in the cell compartments where the targets of the signaling function are located. Other signaling agents are regulated within cells by biosynthesis and breakdown. Since this is impossible in the case of Ca, evolution has selected an entirely different control mechanism, i.e., the reversible complexation by specific proteins, which are either soluble, organized in non membranous structures, or intrinsic to membranes. These proteins “buffer” intracellular Ca at a concentration which is at least 10,000 fold lower than in the external spaces. The functional cycle of cells requires both short and long term regulation of Ca. The rapid and precise modulation is performed by intracel1ular Ca binding proteins but also (in fact mostly, see below) by high Ca affinity membrane intrinsic proteins. The Ca-filtering function of the plasma membrane, which depends on the operation of membrane-intrinsic Ca binding proteins, is responsible for the long term maintenance of the Ca gradient between cells and medium.