Activation by sanguinarine of active sodium efflux from frog skeletal muscle in the presence of ouabain.

1. Applied to intact Na-rich muscle cells, sanguinarine causes an increased 22Na efflux in the presence or absence of extracellular K+ or of ouabain. 2. The increased 22Na efflux does not represent Na:Na exchange as indicated by the fact that it is not associated with an increase in one-way isotopic Na influx nor is it abolished by the absence of external Na+. 3. In both K-free Ringer and K-free Ringer containing ouabain, sanguinarine not only increases one-way efflux of 22Na, it also induces net efflux of Na+ in the face of both an electrical and a concentration gradient. Moreover, the induction of net Na+ efflux occurs in the face of an approximately fourfold increase in PNa. These surprising results lead to the conclusion that, contrary to all experiments, sanguinarine induces active Na+ efflux even in K-free Ringer containing 10(-3) M-ouabain. 4. Sanguinarine depolarizes the Na-loaded muscle to approximately the same value, -54 mV, regardless of the presence or absence of extracellular K+. This depolarization is most likely secondary to the increase in PNa. 5. Sanguinarine causes a net loss of K+, presumably secondary to the depolarization. 6. The stimulation of net Na+ efflux is not correlated with the depolarization. The stimulation in K-free conditions (with or without ouabain), which is associated with the largest depolarization, produces an increment in net Na+ efflux which is not significantly different from the increment in net Na+ efflux in 10 mM-K+ Ringer where the depolarization is smallest. 7. Although sanguinarine increases active Na+ efflux in intact cells, it inhibits the isolated (Na+ + K+)-ATPase, presumably due to interaction with a site on the inner face of the membrane fragment. 8. The surprising stimulation of active Na+ efflux in the presence of 10(-3) M-ouabain must be due to interaction of sanguinarine with a site on the outer face of the membrane, perhaps the K+ activation site. It seems probable that the component of active Na+ efflux induced by sanguinarine is mediated by the Na pump. Sanguinarine may produce a K+-like effect upon the Na pump with consequent unbinding of ouabain.