Calcium in health and disease

Abstract

Evolution has exploited the chemical properties of Ca2+, which facilitate its reversible binding to the sites of irregular geometry offered by biological macro-molecules, to select it as a carrier of cellular signals. A number of proteins bind Ca2+ to specific sites: those intrinsic to membranes play the most important role in the spatial and temporal regulation of the concentration and movements of Ca2+ inside cells. Those which are soluble, or organized in non-membranous structures, also decode the Ca 2+ message to be then transmitted to the targets of its regulation. Since Ca2+ controls the most important processes in the life of cells, it must be very carefully controlled within the cytoplasm, where most of the targets of its signaling function reside. Membrane channels (in the plasma membrane and in the organelles) mediate the entrance of Ca2+ into the cytoplasm, ATPases, exchangers, and the mitochondrial Ca2+ uptake system remove Ca2+ from it. The concentration of Ca2+ in the external spaces, which is controlled essentially by its dynamic exchanges in the bone system, is much higher than inside cells, and can, under conditions of pathology, generate a situation of dangerous internal Ca2+ overload. When massive and persistent, the Ca2+ overload culminates in the death of the cell. Subtle conditions of cellular Ca2+ dyshomeostasis that affect individual systems that control Ca2+, generate cell disease phenotypes that are particularly severe in tissues in which the signaling function of Ca2+ has special importance, e.g., the nervous system. © Springer Science+Business Media Dordrecht 2013.