SUMMARY1. Low concentrations of ouabain which produce a positive inotropic effect on rat ventricular muscle do not inhibit the isolated Na+-K+-ATPase enzyme from this tissue, suggesting that these low-concentration inotropic effects are not related to sodium pump inhibition (Erdmann, Philipp & Scholz, 1980; Adams, Schwartz, Grupp, Grupp, Lee, Wallick, Powell, Twist & Gathiram, 1982).2. We tested this hypothesis by continuously measuring intracellular Na+ activity with Na+-selective micro-electrodes and, separately, twitch tension of rat ventricular muscle during exposure to and wash-out of ouabain.3. Intracellular Na+ activity (a~8) and transmembrane potential of quiescent muscle cells averaged 8-5 + 2-6 mm (mean + S.D., n = 27) and -79-2 + 2-4 mV (n = 34) respectively. 4. Low concentrations of ouabain (0-1, 0-5 and 1-0 #tm) produced concentrationdependent increases in both a'a and twitch tension. At lower concentrations of ouabain (0'01 and 0-05 EM), no detectable changes in aka and twitch tension were observed.5. The data strongly indicate that in rat ventricular muscle sodium pump inhibition is present at low concentrations of ouabain which produce positive inotropy. This is consistent with previous results in canine and sheep cardiac Purkinje fibres.
The role of sodium and calcium ions in strophanthidin inotropy was studied by measuring simultaneously the electrical, mechanical, and intracellular sodium ion activities in electrically driven cardiac Purkinje fibers under conditions that change the intracellular sodium or calcium level (tetrodotoxin, strophanthidin, high calcium, and norepinephrine) . Tetrodotoxin (TTX ; 1-5 X 10 -s M) shifted the action potential plateau to more negative values, shortened the action potential duration, and decreased the contractile tension and the intracellular sodium ion activity (aN.) . The changes in tension and in a N . caused by TTX appear to be related since they had similar time courses . Strophanthidin (2-5 X 10 -7 M) increased tension and aNa less in the presence of TTX, and, for any given value of aN a, 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 X 10 -s M) increased tension and decreased aNa less in the presence than in the absence of TTX . When two of the above procedures were combined, the results were different . Thus, during the increase in aNa and tension caused by strophanthidin in the presence of TTX, increasing calcium or adding norepinephrine increased tension markedly but did not increase aN a further . In a TTX-high calcium or TTX-norepinephrine solution, adding Strophanthidin increased both tension and aNa , and the increase in tension was far greater than in the presence of TTX alone . The results indicate that : (a) the contractile force in Purkinje fibers is affected by a change in aNa ; (b) a decrease in aN a by TTX markedly reduces the inotropic effect of Strophanthidin, possibly as a consequence of depletion of intracellular calcium ; (c) increasing calcium influx with norepinephrine or high calcium in the TTX-Strophanthidin solution produces a potentiation of tension development, even if aN a does not increase further ; and (d) when the calcium influx is already increased by high calcium 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 aNa be associated with suitable calcium availability .
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