Comparison of ATP-dependent calcium transport and calcium-activated ATPase activities of cardiac sarcoplasmic reticulum and sarcolemma from rats of various ages

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Age-associated decline in the Ca 2+ pump function of cardiac sarcoplasmic reticulum (SR), and increase in the Ca 2+ pump activity of sarcolemma (SL) were suggested by my previous study which compared the ATP-energized in vitro Ca 2+ transport activities of these membranes from young (3–4-month-old) and aged (24–25-month-old) rat myocardium ( Biochim. Biophys. Acta, 678 (1981) 442–459). In the present study, ATP-dependent Ca 2+ transport and Ca 2 sensitive ATPase activities of SR and SL derived from the myocardium of rats aged 3 (young), 6 (young adult), 12 (adult), 18 (aging) and 24 (aged) months were determined so as to further characterize age-related changes in the Ca 2+ transport function of these membranes. The rates of ATP-dependent Ca 2+ accumulation by SR from 3- and 6-month-old rats were virtually similar whereas the rates of Ca 2+ accumulation by this membrane from 12-, 18- and 24-month-old rats were significantly lower when compared to 3- or 6-month-old rats; the magnitude of this age-related decline amounted to approx. 18, 45 and 50%, respectively, for SR from 12-, 18- and 24-month-old animals. In contrast to the above findings with SR, SL from 18- and 24-month-old rats displayed substantially higher rates (approx. 45 and 80% increase, respectively, at 18 and 24 months of age) of ATP-dependent Ca 2+ accumulation than SL preparations from 3-, 6- and 12-month-old rats; no significant age-related difference was evident between the latter three age groups. The divergent age-related changes in the Ca 2+ accumulating activities of SR and SL were seen at varying Ca 2+ concentrations (0.54–25.2 μM). With either membrane, kinetic analysis showed that the velocity of Ca 2+ transport, but not the apparent affinity of the transport system for Ca 2+, underwent age-related changes. The Ca 2+-stimulated ATPase activities of SR and SL were not altered significantly with increasing age from 3 to 24 months. Comparison of the ‘combined Ca 2+ transport activity’ of SR and SL from rats of various ages showed a significant overall age-related decline in the rates of Ca 2+ transport via the ATP-driven membrane Ca 2+ pumps; this decrement in membrane function was moderate at 12 months of age (approx. 16%) and became pronounced with advancing age thereafter (approx. 35 and 38%, respectively, at 18 and 24 months of age). Similar progressive age-related decline was observed in the ATP-dependent Ca 2+ sequestering activity of cardiac homogenates. No significant age-related difference was evident in the ATP- and respiration-supported Ca 2+ uptake activity of mitochondria isolated from 6- and 24-month-old rats. The above findings suggest that, barring compensatory age-related increment in Ca 2+ efflux via Na +-Ca + exchange across the SL, the overall ability of the myocardial cell to sequester Ca 2+ from the sarcoplasm declines with aging, mainly due to deterioration in the Ca 2+ pump activity of SR. This impairment in SR function is likely the major factor underlying the prolongation of cardiac relaxation seen with aging. The age-associated decline in the Ca 2+ transport activity of SR may involve uncoupling of the energy transduction and ion translocation functions of this membrane Ca 2+ pump.