Evolution of calcium homeostasis: From birth of the first cell to an omnipresent signalling system

Specific Ca2+ homeostatic system appeared very early in the history of the cell, as a survival system preventing Ca2+-mediated cell damage. This homeostatic system produced a steep (∼20,000 times) concentration gradient between extracellular and intracellular compartments, which has both survival importance (even relatively short increases in cytosolic Ca2+ concentrations higher then 100 nM are incompatible with life) and signalling function. Evolution utilised this gradient together with an ability of Ca2+ to interact with many biological molecules to create the most widespread and versatile signalling system, controlling the majority of cellular processes and executing complex routines of intercellular communications.