Calcium cycling proteins of the cardiac sarcoplasmic reticulum.

nous network within muscle cells, which is the analogue of the endoplasmic reticulum (ER) in other cells. This organelle has a variety of functions, of which release of Ca2+ to the cytosol and reuptake into the interior compartment (the lumen) of the SR are the most important. Rapid release of Ca2+ through a Ca2+ release channel (ryanodine receptor) in the skeletal muscle SR is responsible for muscle contraction: reuptake of Ca2+ by the action of a Ca2+ATPase is responsible for muscle relaxation. In cardiac muscle, however, the intracellular Ca2+ concentration is controlled not only by the SR, but also by other pumps, channels, and exchangers located in the sarcolemma/T-tubules. Nonetheless, the SR of mammalian cardiac cells is well developed and has a major role in the EC coupling.1,2 In the SR of cardiac muscle, as well as in slow-twitch skeletal and smooth muscles, phospholamban (PLN) participates in the EC coupling processes by regulating the activity of the Ca2+-ATPase. Of particular interest is the molecular mode of PLN-mediated regulation of SR Ca2+-ATPase, in which cAMP-dependent protein kinase (PKA)-catalyzed phosphorylation of PLN results in marked augmentation of the Ca2+-ATPase activity.1,3 The molecular structure and function of the 2 important proteins in cardiac SR are highlighted in this review: Ca2+-ATPase and PLN and their molecular interactions, which would help understand the positive and negative inotropic effects ofβ-adrenergic agonist/antagonist. The pathophysiological consequences of molecular perturbation of such a system are also briefly mentioned, leading to an evolving notion that ‘calcium cycling defects’ underlie cardiac hypertrophy and failure.