Calcium ions are important mediators of cell injury. Cytosolic free calcium is maintained at extremely low concentrations (<0.1 ?mol) compared with extracellular levels of 1.3 mmol, and most intracellular calcium is sequestered in mitochondria and endoplasmic reticulum. Such gradients are modulated by membrane-associated, energy-dependent Ca2+, Mg2++-ATPases.

Ischemia and certain toxins cause an early increase in cytosolic calcium concentration, owing to the net influx of Ca2+ across the plasma membrane and the release of Ca2+ from mitochondria and endoplasmic reticulum.

Sustained rises in intracellular Ca2+ subsequently result from nonspecific increases in membrane permeability.

Increased Ca2+ in turn activates a number of enzymes, with potential deleterious cellular effects.

The enzymes known to be activated by calcium include ATPases (thereby hastening ATP depletion), phospholipases (which cause membrane damage), proteases (which break down both membrane and cytoskeletal proteins), and endonucleases (which are responsible for DNA and chromatin fragmentation).

Increased intracellular Ca2+ levels also result in increased mitochondrial permeability and the induction of apoptosis.

Although cell injury often results in increased intracellular calcium and this in turn mediates a variety of deleterious effects, including cell death, loss of calcium homeostasis is not always a proximal event in irreversible cell injury.

See also

 increased cytosolic calcium
 cell injury
 ATP
 adenosine triphosphate