On the mechanism of ouabain toxicity in purkinje and ventricular muscle fibers at rest and during activity

Purkinje and ventricular muscle fibers were loaded with 42 potassium, and tissue radioactivity was measured. At the same time, trans-membrane potentials were recorded. Changes in K fluxes were estimated from the change in tissue radioactivity with the preparation at rest or stimulated electrically. The same procedures were repeated in the presence of ouabain. The results obtained show that ouabain causes (1) a small decrease (about 5 percent) in K uptake in both Purkinje and ventricular muscle fibers at rest; (2) a reduction of about 50 percent of K uptake in stimulated Purkinje fibers; (3) the disappearance of the small increase in K uptake found in stimulated ventricular muscle fibers; (4) a small reduction of K efflux in stimulated Purkinje fibers; (5) a pronounced reduction in K efflux in resting ventricular muscle fibers; and (6) a more frequent inexcitability in Purkinje than in ventricular muscle fibers, although the concentration of ouabain was far smaller for Purkinje fibers. It is concluded that (a) an active fiber is more sensitive than a resting fiber to ouabain toxicity because the usual increase in ionic fluxes (and therefore of active ion transport) with activity is reduced or abolished by ouabain; and (b) Purkinje fibers are more sensitive to ouabain than ventricular muscle fibers because the increase in active ion transport with the onset of stimulation is almost an order of magnitude greater in Purkinje fibers.