THE ROLE OF DICARBOXYLIC ANION TRANSPORT IN THE SLOWER CA2+ UPTAKE IN FETAL CARDIAC SARCOPLASMIC-RETICULUM

Sarcoplasmic reticulum- (SR-)mediated Ca2+ transport is slower in the fetal heart compared with the adult. Virtually all previous studies of cardiac SR Ca2+ transport were performed in the presence of oxalate, a dicarboxylic anion that is cotransported with Ca2+ in skeletal muscle SR. If anion transport is developmentally regulated in cardiac SR, this could explain, in part, the previously reported results. The purposes of this study were to establish the presence of an SR dicarboxylic anion transport process in the rabbit heart and to determine if the perinatal changes in SR Ca2+ transport occur in a dicarboxylic anion-dependent and/or independent manner. In isolated fetal and adult rabbit cardiac SR membranes, we measured Ca2+ ATPase rates and Ca-45(2+) uptake in the presence of the dicarboxylic anions maleate and succinate compared with the zwitterionic buffer PIPES, to which cardiac SR is essentially impermeable. We also measured C-14-succinate uptake by fetal and adult SR membranes. Anion-independent Ca2+ ATPase activity and net Ca-45(2+) uptake were significantly lower in the fetal SR membranes than in the adult. Maleate and succinate increased the Ca2+ ATPase rates in the fetal and adult SR, but the effect was significantly greater in the adult. Maleate and succinate stimulated earlier attainment of maximal net Ca2+ uptake in the fetal and adult SR, suggesting that these dicarboxylic anions stimulated the rate of Ca2+ accumulation. Maleate and succinate significantly increased the maximal net Ca2+ uptake in the adult SR, but not in the fetus. The percentage of stimulation of Ca2+ uptake by maleate and succinate was similar in the fetal and adult SR. Dicarboxylic anion transport, as estimated by C-14-succinate uptake, was significantly lower in the fetus. The previously reported slower Ca2+ uptake rate in the fetus is related to dicarboxylic anion-dependent as well as independent mechanisms. The results provide firm support for the presence of a cardiac SR dicarboxylic anion transport process in rabbits that is developmentally regulated . These results also support the previously reported developmental regulation of the SR Ca2+ pump.