The relationship among intracellular sodium activity, calcium, and strophanthidin inotropy in canine cardiac Purkinje fibers.

Abstract

The role of Na+ and Ca2+ in strophanthidin inotropy was studied by measuring simultaneously the electrical, mechanical, and intracellular Na+ activities in electrically driven cardiac Purkinje fibers under conditions that change the intracellular Na or Ca level (tetrodotoxin, strophanthidin, high Ca, and norepinephrine). Tetrodotoxin (TTX; 1-5 .times. 10-6 M) shifted the action potential plateau to more negative values, shortened the action potential duration, and decreased the contractile tension and the intracellular Na+ activity .**GRAPHIC**. The changes in tension and in .**GRAPHIC**. caused by TTX appear to be related since they had similar time courses. Strophanthidin (2-5 .times. 10-7 M) increased tension and .**GRAPHIC**. less in the presence of TTX, and, for any given value of .**GRAPHIC**. tension was less than in the absence of TTX. Increasing extracellular calcium (from 1.8 to 3.3-3.6 mM) or adding norepinephrine (0.5-1 .times. 10-6 M) increased tension and decreased .**GRAPHIC**. less in the presence than in the absnce of TTX. When 2 of these procedures were combined, the results were different. During the increase in .**GRAPHIC**. and tension caused by strophanthidin in the presence of TTX, increasing Ca or adding norepinephrine increased tension markedly but did not increase .**GRAPHIC**. further. In a TTX-high Ca or TTX-norepinephrine solution, adding strophanthidin increased both tension and .**GRAPHIC**. and the increase in tension was far greater than in the presence of TTX alone. Evidently, the contractile force in Purkinje fibers is affected by a change in .**GRAPHIC**. a decrease in .**GRAPHIC**. by TTX markedly reduces the inotropic effect of strophanthidin, possibly as a consequence of depletion of intracellular Ca; increasing Ca influx with norepinephrine or high Ca in the TTX-strophanthidin solution produces a potentiation of tension development, even if .**GRAPHIC**. does not increase further; when the Ca influx is already increased by high Ca or norepinephrine, strophanthidin has its usual inotropic effect even in the presence of TTX. In conclusion, the positive inotropic effect of strophanthidin requires that an increase in .**GRAPHIC**. be associated with suitable Ca availability.