Regulation of sarcoplasmic reticulum Ca2+ ATPase pump expression and its relevance to cardiac muscle physiology and pathology

Cardiac sarcoplasmic reticulum (SR) Ca(2+) ATPase (SERCA2a) plays a central role in myocardial contractility. SERCA2a actively transports Ca(2+) into the SR and regulates cytosolic Ca(2+) concentration, SR Ca(2+) load, and the rate of contraction and relaxation of the heart. In the heart, SERCA pump activity is regulated by two small molecular weight proteins: phospholamban (PLB) and sarcolipin (SLN). Decreases in the expression levels of SERCA2a have been observed in a variety of pathological conditions. In addition, altered expression of PLB and SLN has been reported in many cardiac diseases. Thus, SERCA2a is a major regulator of intracellular Ca(2+) homeostasis, and changes in the expression and activity of the SERCA pump contribute to the decreased SR Ca(2+) content and cardiac dysfunction during pathogenesis. In this review, we discuss the mechanisms controlling SERCA pump expression and activity both during normal physiology and under pathological states.