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

Abstract

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 .

Negative inotropic effects of disopyramide on guinea‐pig papillary muscles

“…Ouabain has been thought to increase the contraction through a Na+-Ca2+ exchange mechanism (Reuter & Seitz, 1968;Sheu & Fozzard, 1982;Wasserstrom et al, 1983;Eisner et al, 1984;Vassalle & Lee, 1984;Wier & Hess, 1984;Grupp et al, 1985). Ouabain inhibits Na'-K' ATPase and results in an accumulation of [NaJ]i.…”

Intracellular sodium‐calcium dissociation in early contractile failure in hypoxic ferret papillary muscles.

“…Concomitant with this increase in the aia there was an increase in the active tension, and calcium activity (Lee et al 1982;Vassalle & Lee, 1984). Calculation of the sodium activity gradient showed that the sodium driving force decreased significantly during the exposure to ouabain.…”

Effects of caffeine on intracellular sodium activity in cardiac Purkinje fibres: relation to force

“…The preparations were driven at 60 min-' and the stimuli were delivered by a Grass stimulator (model S-4) through a Grass stimulus isolation unit (SIU 4678 (Lee, 1981;Lee & Vassalle, 1983;Vassalle & Lee, 1984). The signals from the Na+ selective and conventional microelectrodes were filtered by means of identical low pass filters (with a fixed frequency of 0.24 Hz) .…”

“…Lee & Vassalle, 1983): the increased Na gradient across the sarcolemma decreases [Ca]i via the Na/Ca exchange. In Table IA Tetrodotoxin (TTX) lowers aiNa (see Vassalle & Lee, 1984) and therefore [Ca]i: force decreases when aiNa decreases (Abete & Vassalle, 1987). In Table IB [Ca].…”