This protein is found as a pentamer and is a major substrate for the cAMP-dependent protein kinase (PKA) in cardiac muscle. phospholamban is an inhibitor of cardiac muscle sarcoplasmic reticulum Ca++-ATPase (SERCA2) in the unphosphorylated state. when phosphorylated (by PKA) - disinhibition of Ca++-ATPase of SR leads to faster Ca++ uptake into the sarcoplasmic reticulum, thereby contributing to the lusitropic response elicited in heart by beta-agonists. The protein is a key regulator ofcardiac diastolic function. Mutations in this gene are a cause of inherited human dilated cardiomyopathy with refractory congestive heart failure.
When phospholamban is phosphorylated by PKA its ability to inhibit the sarcoplasmic reticulum calcium pump (SERCA) is lost. Thus, activators of PKA, such as the beta-adrenergic agonist epinephrine (released by sympathetic stimulation), may enhance the rate of cardiac myocyte relaxation. In addition, since SERCA is more active, the next action potential will cause an increased release of calcium, resulting in increased contraction (positive inotropic effect). When phospholamban is not phosphorylated, such as when PKA is inactive, it can interact with and inhibit SERCA. The overall effect of phospholamban is to decrease contractility and the rate of muscle relaxation, thereby decreasing stroke volume and heart rate, respectively.
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