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.
Periasamy
Muthu
M
Department of Physiology and Cell Biology, College of Medicine and Public Health, The Ohio State University, 304 Hamilton Hall, 1645 Neil Ave, Columbus, OH 43210, USA. periasamy.1@osu.edu
Bhupathy
Poornima
P
Babu
Gopal J
GJ
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000502:physiology; D004734:Energy Metabolism; D015971:Gene Expression Regulation, Enzymologic; D015316:Genetic Therapy; D006801:Humans; D009124:Muscle Proteins / Q000502:physiology; D009200:Myocardial Contraction; D032383:Myocytes, Cardiac / Q000473:pathology* / Q000502:physiology*; D010766:Phosphorylation; D011510:Proteolipids / Q000502:physiology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000502:physiology*; D013974:Thyroxine / Q000502:physiology; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D009124:Muscle Proteins; D011510:Proteolipids; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013974:Thyroxine; D000099211:Phospholamban; C077258:sarcolipin