Molecular regulation of phospholamban function and expression.
Intracellular levels of cAMP regulated by the beta-adrenergic actions of catecholamines play a key in the metabolic, electrical, and mechanical performance of the cardiac muscles. Among a number of biological actions of cAMP, the excitation-contraction coupling process in cardiac myocytes is markedly affected by cAMP through its stimulatory effect on cAMP-dependent protein kinase. Phospholamban, which is expressed in the sarcoplasmic reticulum of cardiac, slow-twitch skeletal, and smooth muscles, is one of the substrates for cAMP-dependent protein kinase. Phospholamban regulates the activity of Ca ATPase in the sarcoplasmic reticulum membranes in a manner dependent on the phosphorylation state of cAMP-dependent protein kinase, thereby changing the mechanical performance of the cardiac muscles. This Ca regulatory mechanism of phospholamban-Ca ATPase system is mediated by a direct protein-protein interaction between two proteins. This review focuses on recent advances in understanding the role of phospholamban molecule in the regulation of Ca transport by cardiac muscle sarcoplasmic reticulum.
Department of Medicine and Pathophysiology, Osaka University Medical School, Osaka, Japan.
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Tada
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Toyofuku