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 fun damental to the control of cardiac contractility. However, the relatio n between Na+-Ca2+ exchange and the control of contractile force has n ot 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 sod ium 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 devel oped tension (DT) increased by 80.2% in adult and by 135.6% in senesce nt 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 an d senescent papillary muscles. During high [Ca2+](o), a(Na)(i) decreas ed 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 < .0 5 vs adult). Simultaneous reduction of [Na+](o) and [Ca2+](o) decrease d 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 m uscles while DT decreased by 22.1% in adult and by only 12.0% in senes cent (p < .01 vs adult) papillary muscles. Simultaneous increase of [N a+](o) and [Ca2+](o) similarly increased a(Na)(i) in both adult senesc ent 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 eq uilibration time for the ratio of external and internal sodium ion act ivities 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+ gradient s modifications associated to changes in contractile force seem to dem onstrate that Na+-Ca2+ exchange is probably not modified by the aging process. However, the slow equilibration time for the ratio of Na+ act ivities might reflect an age-related reduction of the Na+-K+ pump acti vity.