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Strophanthidin inotropy: Role of intracellular sodium ion activity and sodium-calcium exchange

1985; Elsevier BV; Volume: 17; Issue: 11 Linguagem: Inglês

10.1016/s0022-2828(85)80120-6

1095-8584

C. O. Lee, Pasquale Abete, Mark S. Pecker, Jong Kyung Sonn, Mario Vassalle,

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The relation among the ratio of extra- and intra-cellular sodium ion activities (aNa0/aNai), contractile force and action of strophanthidin was studied in cardiac Purkinje fibers when transmembrane Na+ and Ca2+ gradients were changed. The aNai, contractile force and action potential were simultaneously measured. Simultaneous reduction of [Na+]0 and [Ca2+]0 to 80.8 and 1.08 mM respectively, decreased aNai from 8.0±1.1 mM (mean±s.D., n=17) to 6.0±0.9 mM (n=17) whereas contractile force transiently increased and then recovered toward the level similar to that in Tyrode solution. Reduction of [Ca2+]0 alone increased aNai by 1.7±0.4 mM (n=5) and decreased contractile force by 87±5% (n=5). Raising osmolarity of Tyrode solution with sucrose increased both aNai and contractile force. Substitution of sucrose with Na+ (high [Na+] solution) increased aNai by 1.2±0.3 mM (n=5) and decreased contractile force by 31±9% (n=5). Strophanthidin (2×10−7 M) increased aNai by 0.4±0.1 mM (n=6) and contractile force by 24±8 (n=6 in a low [Na+]−[Ca2+] solution. These changes were smaller than those in Tyrode solution (1.1±0.3 mM); 96±32%, n=6). On the other hand, strophanthidin increased aNai and contractile force more in a low [Ca2+] (2.7±0.5 mM; 220±24%, n=5) or a high [Na+] (2.3±0.9 mM; 164±37%, n=5) solution than in Tyrode solution. In the solutions containing the altered [Na+]0 and/or [Ca2+]0, the increases in aNai and force by strophanthidin were parallel. Therefore, the parallel increase in aNai and contractile force due to strophanthidin depends on the initial level of aNai, suggesting the dependence of digitalis inotropy on the rate of Na+ extrusion by the Na+−K+ pump. The results also indicate that the ratio of aNa0/aNai is an important and powerful factor in the control of contractile force. Presumably this is mediated through the Na+−Ca2+ exchange. The relation among the ratio of extra- and intra-cellular sodium ion activities (aNa0/aNai), contractile force and action of strophanthidin was studied in cardiac Purkinje fibers when transmembrane Na+ and Ca2+ gradients were changed. The aNai, contractile force and action potential were simultaneously measured. Simultaneous reduction of [Na+]0 and [Ca2+]0 to 80.8 and 1.08 mM respectively, decreased aNai from 8.0±1.1 mM (mean±s.D., n=17) to 6.0±0.9 mM (n=17) whereas contractile force transiently increased and then recovered toward the level similar to that in Tyrode solution. Reduction of [Ca2+]0 alone increased aNai by 1.7±0.4 mM (n=5) and decreased contractile force by 87±5% (n=5). Raising osmolarity of Tyrode solution with sucrose increased both aNai and contractile force. Substitution of sucrose with Na+ (high [Na+] solution) increased aNai by 1.2±0.3 mM (n=5) and decreased contractile force by 31±9% (n=5). Strophanthidin (2×10−7 M) increased aNai by 0.4±0.1 mM (n=6) and contractile force by 24±8 (n=6 in a low [Na+]−[Ca2+] solution. These changes were smaller than those in Tyrode solution (1.1±0.3 mM); 96±32%, n=6). On the other hand, strophanthidin increased aNai and contractile force more in a low [Ca2+] (2.7±0.5 mM; 220±24%, n=5) or a high [Na+] (2.3±0.9 mM; 164±37%, n=5) solution than in Tyrode solution. In the solutions containing the altered [Na+]0 and/or [Ca2+]0, the increases in aNai and force by strophanthidin were parallel. Therefore, the parallel increase in aNai and contractile force due to strophanthidin depends on the initial level of aNai, suggesting the dependence of digitalis inotropy on the rate of Na+ extrusion by the Na+−K+ pump. The results also indicate that the ratio of aNa0/aNai is an important and powerful factor in the control of contractile force. Presumably this is mediated through the Na+−Ca2+ exchange.