Coordination of cardiac sarcoplasmic reticulum and myofibrillar function by protein phosphorylation.
Adrenergic stimulation alters functional dynamics of the heart by mechanisms most likely involving cyclic AMP (cAMP)-dependent protein phosphorylation. In vitro studies indicate that the myofibrils and sarcoplasmic reticulum (SR) may act as effectors of the adrenergic stimulation. cAMP-dependent phosphorylation of troponin I (TnI), one of the regulatory proteins of cardiac myofibrils, results in a decreased steady-state affinity of troponin C (TnC) for calcium, an increase in the off-rate for Ca2+ exchange with TnC, and a rightward shift of the relation between free Ca2+ and myofibrillar force or ATPase. Phosphorylation of phospholamban, a regulatory protein of cardiac SR, results in an increased velocity of Ca2+ transport by SR vesicles, an increased affinity of the transport protein for Ca2+, and an increased turnover of elementary steps of the ATPase reaction. These in vitro findings support the hypothesis that the inotropic response of the heart to catecholamine stimulation involves phosphorylation of TnI and phospholamban. Our in vivo studies with perfused rabbit hearts show that during the peak of the inotropic response to isoproterenol there is a simultaneous phosphorylation of TnI and an 11,000-dalton protein in the SR, most likely the monomeric form of phospholamban.
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002135:Calcium-Binding Proteins / Q000502:physiology; D002147:Calmodulin / Q000502:physiology; D002395:Catecholamines / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D007425:Intracellular Membranes / Q000502:physiology; D008565:Membrane Proteins / Q000502:physiology*; D008970:Molecular Weight; D009200:Myocardial Contraction; D009206:Myocardium / Q000378:metabolism*; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D014336:Troponin / Q000502:physiology; D000099211:Phospholamban
D002118:Calcium; D002135:Calcium-Binding Proteins; D002147:Calmodulin; D002395:Catecholamines; D000242:Cyclic AMP; D008565:Membrane Proteins; D014336:Troponin; D000099211:Phospholamban