Phospholamban and cardiac contractility.
Over the last three decades, our knowledge and understanding of the role of phospholamban and its modulation of sarcoplasmic reticulum (SR) function has advanced significantly. Phospholamban is a key regulator of cardiac contractility and modulates SR Ca2+ sequestration by inhibiting the SR Ca2+-ATPase (SERCA) in its dephosphorylated state. Upon phosphorylation, which is mediated through beta-adrenergic stimulation, the inhibitory effect of phospholamban on the function of SERCA is relieved. This review summarizes recent advances that have been made towards understanding the modulation of SR Ca2+-sequestration by phospholamban through the generation and characterization of genetically altered animal models. It also discusses the role of phospholamban in human heart failure and recent attempts to restore SR function in experimentally induced and human heart failure, which may be translated into future therapeutic approaches in the treatment of this disease.
Frank
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Department of Pharmacology and Cell Biophysics, University of Cincinnati, College of Medicine, OH 45267-0575, USA.
Kranias
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D000818:Animals; D002135:Calcium-Binding Proteins / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors; D018390:Gene Targeting; D006333:Heart Failure / Q000503:physiopathology; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009200:Myocardial Contraction; D012519:Sarcoplasmic Reticulum / Q000502:physiology; D000099211:Phospholamban
D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D000099211:Phospholamban