Relation between intracellular sodium and twitch tension in sheep cardiac Purkinje strands exposed to cardiac glycosides

Changes in intracellular sodium ion activity (a(Na)(i)) produced by several cardiac glycosides were correlated with twitch tension in sheep cardiac Purkinje strands. Simultaneous measurements of (a(Na)(i)) and twitch tension were obtained through the use of Na-sensitive intracellular microelectrodes (ETH 227) in Purkinje preparations stimulated at a frequency of 1 Hz. All concentrations of ouabain, acetylstrophanthidin, and actodigin that were tested caused an increase in (a(Na)(i)) immediately before, or coincident with, a positive inotropic effect. No fall in (a(Na)(i)) was observed at any positive inotropic concentration of digitalis in these beating fibers. In all cases, the onset and washout of the positive inotropic effect were paralleled by the rise and fall in (a(Na)(i)) respectively. No dissociation between changes in (a(Na)(i)) and twitch tension occurred at any concentration of the agents used. The relation between changes in (a(Na)(i)) and twitch tension was linear with 1 mM increase in (a(Na)(i)) producing about a 100% increase in twitch magnitude. Propranolol did not significantly alter this relationship. The increase in (a(Na)(i)) with digitalis was also associated with a reduction in the maximum depolarization rate of the action potential, presumably as a consequence of a reduction in the transmembrane Na electrochemical gradient. These results indicate that the positive inotropic action of digitalis in sheep Purkinje strands is always associated with a rise in (a(Na)(i)) secondary to inhibition of the Na pump. This increase in (a(Na)(i)) could increase calcium available for contraction via the Na-Ca equilibrium exchange process. In addition, the increase in (a(Na)(i)) reduces V̇(max), as a consequence of decreasing the electrochemical gradient for Na.