Inhibition of ouabain-induced increase in Na content of cultured myocardial cells by quinidine and procainamide.

Addition of ouabain caused gradual increases of both the Na content of cultured myocardial cells and the rate of Ca++ uptake by the cells. Ouabain-induced irregular beating of the cells (ouabain toxicity) appeared to develop when the Na content and the rate of Ca++ uptake exceeded about 1.5 and 2.0 times, respectively, the normal levels. Quinidine and procainamide prevented ouabain-induced increases of the Na content and the rate of Ca++ uptake as well as ouabain-induced toxicity. The problem of how quinidine and procainamide counteract the effects of ouabain was then studied. Quinidine and procainamide did not affect the Na+-Ca++ exchange activity. Na+,K+-adenosine triphosphatase activity, Na+-pumping out activity or ouabain-binding activity of myocardial cells, but inhibited passive Na+ influx, which is achieved by a simple diffusion system. From these observations, it is suggested that inhibition by quinidine or procainamide of passive Na+ influx indirectly prevents ouabain-induced increase in the intracellular Na content of myocardial cells and that this presumably explains at least in part the inhibitory effect of quinidine and procainamide on ouabain-induced irregular beating.