Influence of age and run training on cardiac Na /Ca exchange

Mace, Lisa C., Bradley M. Palmer, David A. Brown, Korinne N. Jew, Joshua M. Lynch, Jason M. Glunt, Todd A. Parsons, Joseph Y. Cheung, and Russell L. Moore. Influence of age and run training on cardiac Na / Ca2 exchange. J Appl Physiol 95: 1994–2003, 2003. First published July 25, 2003; 10.1152/japplphysiol.00551.2003.— 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; 8to 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 agerelated 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 (Nain /Caout 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 (Vm) 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.