ALTERATIONS IN SARCOPLASMIC-RETICULUM CALCIUM-UPTAKE, RELAXATION PARAMETERS AND THEIR RESPONSES TO BETA-ADRENERGIC AGONISTS IN THE DEVELOPING RABBIT HEART

Developmental changes in cardiac sarcoplasmic reticulum function, whic h may reflect alterations in the myocardial rate of relaxation and its responses to beta-adrenergic stimulation, were assessed using fetal, 4-day-old, 21-day-old and adult rabbit hearts. The fetal hearts exhibi ted the slowest rate of relaxation (-dP/dt) and the lowest V-max and E C(50) of the sarcoplasmic reticulum Ca2+-pump for Ca2+ compared to the other age groups. These parameters were similar among the 4-day-old, 21-day-old and adult hearts, The low physiological and biochemical par ameters in the fetal hearts reflected reduced levels of expression of the sarcoplasmic reticulum Ca2+-pump and its inhibitor, phospholamban, assessed by quantitative immunoblotting. Isoproterenol perfusion of f etal hearts had no significant effect on their relaxation parameters o r on the EC(50) of the Ca2+-pump for Ca2+, consistent with the low rel ative levels of phospholamban expressed in these hearts. However, perf usion of the 4-day-old, 21-day-old and adult hearts with isoproterenol resulted in significant increases in the rates of relaxation of each group. The increases in relaxation parameters were associated with dec reases in the EC(50) of the cardiac sarcoplasmic reticulum Ca2+-pump f or Ca2+ suggesting a phosphorylation-mediated relief of the phospholam ban inhibitory effects. These findings indicate that developmental reg ulation of the levels of the activity of the cardiac sarcoplasmic reti culum Ca2+-pump may reflect alterations in cardiac relaxation paramete rs and their modulation by beta-adrenergic agonists. (C) 1995 Academic Press Limited