Alterations in sarcoplasmic reticulum cakcium uptake, relaxation parameters and their responses to β-adrenergic agonists in the developing rabbit heart

Developmental changes in cardiac sarcoplasmic reticulum function, which may reflect alterations in the myocardial rate of relaxation and its responses to β-adrenergic stimulation, were assessed using fetal, 4-day-old, 21-day-old and adult rabbit hearts. The fetal hearts exhibited the slowest rate of relaxation ( −dP/dt) and the lowest Vmax and EC550 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 parameters in the fetal hearts reflected reduced levels of expression of the Sarcoplasmic reticulum Ca2+-pump and its inhibitor, phospholamban, assessed by quantitative immunoblotting. lsoproterenol perfusion of fetal hearts had no significant effect on their relaxation parameters or on the ECS50 of the Ca2+-pump for Ca 2+ consistent with the low relative levels of phospholamban expressed in these hearts. However. perfusion 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 decreases in the EC50 of the cardiac Sarcoplasmic reticulum Ca2+-pump for Ca2+, suggesting a phosphorylation-mediated relief of the phospholamban inhibitory effects. These findings indicate that developmental regulation of the levels of the activity of the cardiac sarcoplasmic reticulum Ca2+-pump may reflect alterations in cardiac relaxation parameters and their modulation by β-adrenergic agonists.