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1 Department of Integrative Physiology, University of Colorado at Boulder, Boulder, CO, USA
2 University of Vermont, Burlington, VT, USA
3 Weiss Research Center, Danville, PA, USA
* To whom correspondence should be addressed. E-mail: Rmoore{at}colorado.edu.
The effects of age and training on myocardial Na+-Ca2+ exchange were examined in sedentary young (YS; 14-15 mo), aged sedentary (AS; 27-31 mo) and aged trained (AT; 8-11 wk treadmill run training) male Fischer Brown Norway rats. Both 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 isolated from AT rats. At the single cardiocyte level, late action potential (AP) duration was prolonged, resting membrane potential was more positive, and overshoot potential was greater in cardiocytes isolated from AS rats relative to cardiocytes isolated from YS rats (P<0.05). Training did not influence any of these age-related AP characteristics. In electrically paced cardiocytes, neither shortening nor intracellular [Ca2+] ([Ca2+]i) dynamics were influenced by age or training. Similarly, neither age nor training influenced the rate of [Ca2+]i clearance via forward (Na+in/Ca2+out) Na+-Ca2+ exchange following caffeine-induced Ca2+ release from the sarcoplasmic reticulum, or in cardiac sodium-calcium 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 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 AP prolongation that we observed in this study.
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