Influence of age and run training on cardiac Na+/Ca2+ exchange

Effects of age and training on myocardial Na+/Ca2+ exchange were examined in young sedentary (YS; 14 - 15 mo), aged sedentary (AS; 27 - 31 mo), and aged trained (AT; 8- to 11-wk treadmill run training) male Fischer Brown Norway rats. Whole heart performance and isolated cardiocyte Na+/ Ca2+ exchange characteristics were measured. At the whole heart level, a small but significant slowing of late isovolumic left ventricular (LV) relaxation, which may be indicative of altered Na+/Ca2+ exchange activity, was seen in hearts from AS rats. This subtle impairment in relaxation was not observed in hearts from AT rats. At the single-cardiocyte level, late action potential duration was prolonged, resting membrane potential was more positive, and overshoot potential was greater in cardiocytes from AS rats than from YS rats ( P < 0.05). Training did not influence any of these age-related action potential characteristics. In electrically paced cardiocytes, neither shortening nor intracellular Ca2+ concentration ([Ca2+](i)) dynamics was influenced by age or training. Similarly, neither age nor training influenced the rate of [Ca2+](i) clearance via forward (Na-in(+)/Ca-out(2+)) Na+/Ca2+ exchange after caffeine-induced Ca2+ release from the sarcoplasmic reticulum or cardiac Na+/Ca2+ exchanger protein (NCX1) expression. However, when whole cell patch-clamp techniques combined with fluorescence microscopy were used to evaluate the ability of Na+/Ca2+ exchange to alter cytosolic [Ca2+] ([Ca2+](c)) under conditions where membrane potential (V-m) and internal and external [Na+] and [Ca2+] could be controlled, we observed age-associated increases in forward Na+/ Ca2+ exchange-mediated [Ca2+](c) clearance (P < 0.05) that were not influenced by training. The age-related increase in forward Na+/Ca2+ exchange activity provides a hypothetical explanation for the late action potential prolongation observed in this study.