The signaling function of calcium and its regulation.

CALCIUM COMPLEXATION WITH SOLUBLE PROTEINS: The signaling function of calcium is controlled by reversible complexation to specific proteins. Most of the soluble proteins belong to the exchange factor (EF)-hand family and act as decoders of the calcium information. They do so by changing conformation twice, once upon complexing calcium and later, upon interacting with target enzymes. The most important among the EF-hand proteins is calmodulin. MEMBRANE-INTRINSIC CALCIUM-CONTROLLING PROTEINS: Other calcium-controlling proteins are membrane-intrinsic (plasma membranes and organelles), and interact with calcium with high affinity (pumps) or with low affinity (sodium-calcium exchange, calcium channels, electrophoretic uptake by mitochondria). The fine and rapid tuning of cellular calcium is performed essentially by pumps, although in excitable tissues, plasma membrane sodium-calcium exchange is also important. Long-term, low-affinity calcium regulation, particularly in the presence of pathological increases in calcium entry, is probably performed by mitochondrial uptake/release systems.