The role of calcium in cell death

Abstract Cell death is frequently encountered in human disease. Ischemia, chemicals, viruses, radiation and toxins are among its varied causes. The resulting pathology, however, is very uniform. The common pattern of altered morphology, coagulative necrosis, implies that, at some point, the diverse causes share common mechanisms. Recent evidence suggests that coagulative necrosis may ultimately reflect an alteration in the control of intracellular calcium homeostasis. Studies in intact animals and in cell culture suggest than an ultimate influx of calcium ions across injured plasma membranes and along a steep concentrations gradient converts potentially reversible alterations into the irreversible injury of cell death. The structural alterations in cellular constituents that characterize coagulative necrosis are themselves very likely the direct result of the action of an elevated calcium concentration on cellular macromolecules. The continuing need to identify the membrane alterations induced by the various causes of cell death in order to assess their potential reversibility in the absence of irreversible calcium accumulation is emphasized.