When phospholamban is phosphorylated by PKA, its ability to inhibit SERCA2 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 SERCA2 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.
Gene knockout of phospholamban results in animals with hyperdynamic hearts, with little apparent negative consequence.
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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". Science. 299 (5611): 1410–3. doi:10.1126/science.1081578. PMID12610310.
↑Tada M, Kirchberger MA, Repke DI, Katz AM (October 1974). "The stimulation of calcium transport in cardiac sarcoplasmic reticulum by adenosine 3':5'-monophosphate-dependent protein kinase". J Biol Chem. 249 (19): 6174–80. PMID4371608.
↑ 12.012.1Asahi, 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.
↑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.