THERAPEUTIC AND TOXIC EFFECTS OF OUABAIN ON K⁺ FLUXES IN RABBIT ATRIA

¹ Department of Pharmacology, State University of New York, Upstate Medical Center, Syracuse, New York

Previous experiments with stimulated rabbit atria have indicated that "therapeutic" positive inotropic concentrations of ouabain maintain intracellular K⁺ in vitro and produce no change in vivo. "Toxic" negative inotropic concentrations on the other hand decrease intracellular K⁺ concentration. Neither the toxic nor therapeutic effects on K⁺ as determined by terminal analysis of the tissue could be correlated with changes in excitability or contractility. This experiment was undertaken to measure changes in K⁺ fluxes during exposure to "toxic" or "therapeutic" concentrations of ouabain.

In isolated rabbit atria "therapeutic" concentrations of ouabain decreased K⁴² loss as well as increased uptake of radioactive potassium. This may explain both the maintenance and increase in intracellular K⁺ observed by other investigators. "Toxic" concentrations of ouabain blocked K⁴² uptake and this alone may explain the effects of digitalis on intracellular K⁺ concentration. However, the inhibition of K⁺ uptake occurred later than the negative inotropic effect on contractility. This supports the previous assumption (Tuttle et al., 1961) that changes in intracellular K⁺ concentration or fluxes brought about by ouabain are not causally related to the inotropic effects of the drug.