Developmental changes in cardiac sarcoplasmic reticulum in sheep

Physiologic studies suggest that the myocardium from fetal and newborn sheep functions at a higher contractile state with decreased contractile reserve when compared to the myocardium of adult sheep. To investigate the role of Ca²⁺ transport by the sarcoplasmic reticulum (SR) in this phenomenon, we studied functional properties and protein composition of cardiac SR vesicles isolated from fetal and maternal sheep. Active accumulation of Ca²⁺ and the density of the Ca²⁺ pump protein were decreased 60% (p<0.01) in fetal SR vesicles; however Ca²⁺-dependent ATPase activity was decreased only 30% (p<0.01). This decreased difference in Ca²⁺-dependent ATPase activities was accounted for by the higher turnover number measured for the Ca²⁺ pump of fetal SR vesicles (1.6-fold increased, p<0.01). Ryanodine, an alkaloid which blocks Ca²⁺ efflux from cardiac SR vesicles, stimulated Ca²⁺ uptake more effectively in fetal SR vesicles, suggesting that these vesicles had a higher passive Ca²⁺ permeability during conditions of active Ca²⁺ transport. Protein compositional studies showed that the content of phospholamban was decreased in fetal SR vesicles and was correlated with the decrease in the density of Ca²⁺ pumps. In contrast, the content of calsequestrin and the density of [³H]nitrendipine-binding sites were increased approximately 2-fold in fetal SR vesicles. These functional and compositional differences between SR vesicles isolated from fetal and maternal sheep may indicate that there is relatively more junctional SR in fetal hearts. Since the SR regulates muscle contraction by modulating intracellular Ca²⁺ concentration, it is possible that developmental alternations in cardiac SR may contribute to the decreased myocardial contractile reserve noted in fetal sheep.