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 macromolecules, 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 Ca²⁺ 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.

Please cite as: Met. Ions Life Sci. 13 (2013) 81–137