Effects of aging on phospholamban phosphorylation and calcium transport in rat cardiac sarcoplasmic reticulum.
Acceleration of cardiac relaxation upon beta adrenergic stimulation is due, in part, to enhancement in the rate of Ca2+ sequestration by the sarcoplasmic reticulum (SR) Ca2+ pump resulting from cAMP-mediated phosphorylation of the SR protein phospholamban. Our previous studies have shown that in rat myocardium, beta adrenergic activation of adenylate cyclase and the Ca2+ pump activity of SR decline with aging (Mech. Ageing Dev., 19 (1982) 127-139; 38 (1987) 127-143). In the present study, the effect of aging on phospholamban phosphorylation and consequent changes in SR Ca2+ pump activity were evaluated using cardiac SR from 6 (young adult), 12 (adult) and 28 (aged) months old rats. No age-related differences were observed in the rate or maximum level of phospholamban phosphorylation by exogenous cAMP-dependent protein kinase. The rates of ATP-dependent Ca2+ uptake by SR from young adult and aged rats were stimulated upon phospholamban phosphorylation, the percentage stimulation of Ca2+ uptake at varying Ca2+ concentrations (0.24-11.9 microM) was not diminished with aging. However, the rates of Ca2+ uptake by phosphorylated and unphosphorylated SR were remarkably lower (35-50%) in the aged. Regardless of the age of rats, the stimulatory effect of phosphorylation on Ca2+ uptake by SR was due to increase in Vmax of Ca2+ transport with no appreciable changes in K0.5 for Ca2+. These findings imply that in spite of the age-associated decline in SR Ca2+ pump activity, the ability of phospholamban to undergo cAMP-mediated phosphorylation and the relative responsiveness of the SR Ca2+ pump to phospholamban phosphorylation are not diminished in the aging heart.
Jiang
M T
MT
Department of Physiology, University of Western Ontario, London, Canada.
Narayanan
N
N
D000255:Adenosine Triphosphate / Q000502:physiology; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D009994:Osmolar Concentration; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D012519:Sarcoplasmic Reticulum / Q000378:metabolism*; D000099211:Phospholamban
D000255:Adenosine Triphosphate; D002118:Calcium; D002135:Calcium-Binding Proteins; D011494:Protein Kinases; D000099211:Phospholamban