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

¹Department of Integrative Physiology, University of Colorado at Boulder, Boulder, Colorado 80309-0354; ²University of Vermont, Burlington, Vermont 05405; and ³Weis Research Center, Danville, Pennsylvania 17822

Submitted 23 May 2003 ; accepted in final form 21 July 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; 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_out²⁺) 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.

caffeine; NCX1; Fisher Brown Norway rat; treadmill; heart; cardiocyte; calcium; sodium

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