This protein is found as a pentamer and is a major substrate for the cAMP-dependent protein kinase (PKA) in cardiac muscle. The protein is an inhibitor of cardiac muscle sarcoplasmic reticulum Ca++-ATPase (SERCA) in the unphosphorylated state, but inhibition is relieved upon phosphorylation of the protein. The subsequent activation of the Ca++ pump leads to shorter intervals between contractions, thereby contributing to the lusitropic response elicited in heart by beta-agonists. The protein is a key regulator of cardiac 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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^Schmitt JP, Kamisago M, Asahi M, Li GH, Ahmad F, Mende U, Kranias EG, MacLennan DH, Seidman JG, Seidman CE (February 2003). "Dilated cardiomyopathy and heart failure caused by a mutation in phospholamban". Science299 (5611): 1410–3. doi:10.1126/science.1081578. PMID12610310.
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^ abAsahi, Michio; Kurzydlowski Kazimierz, Tada Michihiko, MacLennan David H (Jul 2002). "Sarcolipin inhibits polymerization of phospholamban to induce superinhibition of sarco(endo)plasmic reticulum Ca2+-ATPases (SERCAs)". J. Biol. Chem. (United States) 277 (30): 26725–8. doi:10.1074/jbc.C200269200. ISSN0021-9258. PMID12032137.Cite uses deprecated parameters (help)
^Asahi, M; Kimura Y, Kurzydlowski K, Tada M, MacLennan D H (Nov 1999). "Transmembrane helix M6 in sarco(endo)plasmic reticulum Ca(2+)-ATPase forms a functional interaction site with phospholamban. Evidence for physical interactions at other sites". J. Biol. Chem. (UNITED STATES) 274 (46): 32855–62. doi:10.1074/jbc.274.46.32855. ISSN0021-9258. PMID10551848.Cite uses deprecated parameters (help)