CHANGES IN CALCIUM-UPTAKE RATE BY RAT CARDIAC MITOCHONDRIA DURING POSTNATAL-DEVELOPMENT

Ca2+ uptake, transmembrane electrical potential (Delta psi m) and oxyg en consumption were measured in isolated ventricular mitochondria of r ats from 3 days to 5 months of age. Estimated values of ruthenium red- sensitive, succinate-supported maximal rate of Ca2+ uptake (V-max, exp ressed as nmol Ca2+/min/mg protein) were higher in neonates and gradua lly fell during postnatal development (from 475+/-24 at 3-6 days, to 1 56+/-10 in adults, P<0.001), whereas K-0.5 values (similar to 10 mu M) were not significantly affected by age. Under similar conditions, mit ochondria from adults (5 months old) and neonates (4-6 days old) showe d comparable state 4 (succinate and alpha-ketoglutarate as substrates) and state 3(ADP) (alpha-ketoglutarate-supported) respiration rates, a s well as Delta psi m values (similar to-150 mV). Respiration-indpende nt Delta psi m and Ca2+ uptake, supported by valinomycin-induced K+ ef flux were also investigated at these ages. A transient Delta psi m (si milar to-30 mV) was evoked by valinomycin in both neonatal and adult m itochondria. Respiration-independent Ca2+ uptake was also transient, b ut its initial rate was significantly higher in neonates than in adult s (49.4+/-10.0 v 28.0+/-5.7 mmol Ca2+/min/mg protein, P<0.01). These r esults indicate that Ca2+ uptake capacity of rat cardiac mitochondria is remarkably high just after birth and declines over the first weeks of postnatal life, without change in apparent affinity of the transpor ter. Increased mitochondrial Ca2+ uptake rate in neonates appears to b e related to the uniporter itself, rather than to modification of the driving force of the transport. (C) 1998 Academic Press.