Relation of sodium pump inhibition to positive inotropy at low concentrations of ouabain in rat heart muscle

Abstract

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). 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. Intracellular Na+ activity (aiNa) 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. Low concentrations of ouabain (0.1, 0.5 and 1.0 microM) produced concentration-dependent increases in both aiNa and twitch tension. At lower concentrations of ouabain (0.01 and 0.05 microM), no detectable changes in aiNa and twitch tension were observed. 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.