The role of phospholamban in the regulation of calcium transport by cardiac sarcoplasmic reticulum.
The calcium transport mechanism of cardiac sarcoplasmic reticulum (SR) is (SR) is regulated by a phosphoregulatory mechanism involving the phosphorylation-dephosphorylation of an integral membrane component, termed phospholamban. Phospholamban, a 27,000 Da proteolipid, contains phosphorylation sites for three independent protein kinases: 1) cAMP-dependent, 2) Ca2(+)-calmodulin-dependent, and 3) Ca2(+)-phospholipid-dependent. Phosphorylation of phospholamban by any one of these kinases is associated with stimulation of the calcium transport rates in isolated SR vesicles. Dephosphorylation of phosphorylated phospholamban results in the reversal of the stimulatory effects produced by the protein kinases. Studies conducted on perfused hearts have shown that during exposure to beta-adrenergic agents, a good correlation exists between the in situ phosphorylation of phospholamban and the relaxation of the left ventricle. Phosphorylation of phospholamban in situ is associated with stimulation of calcium transport rates by cardiac SR, similar to in vitro findings. Removal of beta-adrenergic agents results in the reversal of the inotropic response and this is associated with dephosphorylation of phospholamban. These findings indicate that a phospho-regulatory mechanism involving phospholamban may provide at least one of the controls for regulation of the contractile properties of the myocardium.
Davis
B A
BA
Department of Pharmacology and Cell Biophysics, University of Cincinnati, College of Medicine, Ohio 45267-0575.
Edes
I
I
Gupta
R C
RC
Young
E F
EF
Kim
H W
HW
Steenaart
N A
NA
Szymanska
G
G
Kranias
E G
EG
D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D009206:Myocardium / Q000378:metabolism*; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D007545:Isoproterenol; D010744:Phosphoric Monoester Hydrolases; D011494:Protein Kinases; D011943:Receptors, Adrenergic, beta; D000099211:Phospholamban