The role of aging on the control of contractile force by Na+-Ca2+ exchange in rat papillary muscle

Background. Sarcolemmal Na+-Ca2+ exchange system is believed to be fundamental to the control of cardiac contractility. However, the relation between Na+-Ca2+ exchange and the control of contractile force has not been studied in senescent myocardium. Methods. The role of Na+-Ca2+ exchange in the regulation of the cardiac muscle's contractile force was studied in adult and senescent papillary muscles by simultaneously measuring intracellular sodium activity (a(Na)(i)), action potential,and contractile force while varying extracellular concentration of sodium and/or calcium. Results. Reduction of [Na+](o) decreased a(Na)(i) from 8.0 +/- 1.8 to 4.1 +/- 0.8 in adult (-3.9 mM) and from 8.7 +/- 1.9 to 4.7 +/- 0.9 in senescent (-4.0 mM) papillary muscles, while developed tension (DT) increased by 80.2% in adult and by 135.6% in senescent papillary muscles (p < .01 vs adult). During low [Ca2+](o) and high [Na+](o), a(Na)(i) and DT modifications were similar both in adult and senescent papillary muscles. During high [Ca2+](o), a(Na)(i) decreased to a similar extent in both adult and senescent papillary muscles, while DT increased by 37.8% in adult and by 67.8% in senescent (p < .05 vs adult). Simultaneous reduction of [Na+](o) and [Ca2+](o) decreased a(Na)(i) from 8.1 +/- 1.2 to 6.8 +/- 1.1 mM in adult (-1.3 mM), and from 8.4 +/- 1.0 to 7.2 +/- 1.0. mM in senescent (-1.2 mM) papillary muscles while DT decreased by 22.1% in adult and by only 12.0% in senescent (p < .01 vs adult) papillary muscles. Simultaneous increase of [Na+](o) and [Ca2+](o) similarly increased a(Na)(i) in both adult senescent papillary muscles, but decreased DT by 28.5% in adult and by 11.7% in senescent (p < .01 vs adult). After [Na+](o) modifications, the equilibration time for the ratio of external and internal sodium ion activities was slowed in senescent papillary muscles (i.e., in low [Na+](o) solution the equilibration time was 4.6 +/- 0.9 min in adult and 6.3 +/- 1.2 min in senescent papillary muscles, p < .001). Conclusions. Similar changes of a(Na)(i) during transmembrane Na+ and Ca2+ gradients modifications associated to changes in contractile force seem to demonstrate that Na+-Ca2+ exchange is probably not modified by the aging process. However, the slow equilibration time for the ratio of Na+ activities might reflect an age-related reduction of the Na+-K+ pump activity.