SR Ca2+-ATPase (SERCA)

The SERCA pump, a 110-kDa transmembrane protein, is the major regulator of Ca2+ homeostasis and contractility in cardiac and skeletal muscle. Five isoforms of SERCA genes have been isolated, and the cardiac/slow skeletal muscle type splicing variant of the SERCA2a gene is the predominant SERCA isotype expressed in both normal and failing hearts. The Ca2+ re-uptake function of the SR is mainly regulated by the SERCA2a pump. SERCA2a plays a central role in SR Ca2+ handling required for excitation–contraction coupling in the heart. The expression levels and activity of SERCA2a are critical determinants of cardiac function. Decreases in SERCA2a gene expression levels and activity were observed in several animal heart failing models and in human failing cardiomyocytes, correlating with the defects in SR Ca2+-uptake function in these models. The role of SERCA2a in cellular function and the modulation of SERCA2a activity by PLN have been examined by utilizing in vitro adenoviral-mediated gene transfer and transgenic approaches by our lab and others. These studies suggest that there is a direct correlation between SERCA2a levels and modulation of cardiac contractility and further support the notion that SERCA2a function is one of the fundamental determinants of cardiac contractility (See Figure Below).

Effect of expression levels of SERCA on Ca2+ uptake.