Regulation of Cardiac Sarco(endo)plasmic Reticulum Calcium-ATPases (SERCA2a) in Response to Exercise

Sarco(endo)plasmic reticulum calcium ATPase (SERCA2a) plays an integral role in Ca2+ cycling in the heart. After a myocardial contraction has occurred, SERCA2a is primarily responsible for transporting Ca2+ out of the cytosol into the sarcoplasmic reticulum. Consequently, SERCA2a is key in determining relaxation time and inotropy of subsequent contractions. There are ten different SERCA isoforms in the body, where SERCA2a is the isoform expressed in the heart. Both SERCA2a expression and activity are reduced in models of disease. As such, a large body of research has examined SERCA2a and how it might be used as a means to restore heart function in models of disease. In this chapter, we examine various regulatory mechanisms of SERCA2a and how these mechanisms affect SERCA2a and cardiac function. Transcriptional, protein (e.g., phospholamban and sarcolipin), hormonal (e.g., thyroid hormone and adiponectin), and posttranslational modification (e.g., nitration, glutathionylation, SUMOylation, acetylation, glycosylation, and O-glcNAcylation) processes as they regulate SERCA2a are discussed. Additionally, exercise and its effect on the regulatory mechanisms of SERCA2a is examined.