Regulation of calcium transport in cardiac cells

Calcium transporting systems and the regulatory events accompanying them are pivotal in the function of the cardiac cell. The concerted involvement of the various membranes achieve cellular calcium homeostasis that can also respond to the physiological exigencies of the cell. Three membrane systems are primarily involved; the sarcolemma, sarcoplasmic reticulum, and the mitochondria. The various Ca2+ transport systems that have been described in these membranes are as follows: the calcium channel, Ca2+-ATPase, Ca2+-Mg2+ ATPase, and sodium-calcium exchanger in the sarcolemma; the Ca2+-Mg2+ ATPase and a possible calcium channel in the sarcoplasmic reticulum; and the sodium-calcium exchanger and electrophoretic calcium uniporter in the mitochondrial inner membrane. These systems mediate calcium fluxes to maintain physiological cytosolic calcium concentrations. beta-Adrenergic hormones regulate calcium transport systems in sarcolemma and sarcoplasmic reticulum, while alpha-adrenergic hormones modulate those in the mitochondria and probably in the sarcolemma. The response to these hormones is initiated at the sarcolemma, which contains the specific receptors. Intracellularly the effects are propagated by secondary messengers, e.g., cAMP, calcium, and lipid changes. Specific proteins are also involved in these events. Phospholamban, a 22 000 dalton protein, is involved in mediating the cAMP-dependent inotropic effects, by activating the Ca2+-Mg2+ ATPase of the sarcoplasmic reticulum. Alterations in any one of the systems involved in the regulation of calcium transport or in the calcium transport systems per se, would then result in drastic alterations in the cellular calcium homeostasis. Such effects could be of significance in cellular dysfunction during cardiac disease.