Interaction between potassium concentration and inhibition of myocardial Na(+)-K(+)-ATPase by two class 1A antiarrhythmic drugs: quinidine and procainamide.

The inhibitory actions of quinidine and procainamide on the Mg(2+)-dependent ATP hydrolytic action of myocardial Na(+)-K(+)-ATPase (EC 3.6.1.3) were studied in guinea-pig heart preparations incubated in media containing 2.5, 5 and 10 mM of K+. The IC50 values for quinidine were 0.23 +/- 0.02 mM at 2.5 mM K+, 0.56 +/- 0.18 mM at 5 mM K+ and 0.82 +/- 0.05 mM at 10 mM K+, and those of procainamide were 7.2 +/- 1.8 mM at 2.5 mM K+, 13.7 +/- 2.3 mM at 5 mM K+ and 35.5 +/- 3.3 mM at 10 mM K+. Thus, reducing the K+ concentration from the "standard" 5 mM to 2.5 mM showed a significant right-to-left shift in the inhibitory potencies of the drugs, while increasing it to 10 mM resulted in opposite effects. The results show that the inhibitory actions of both drugs on the ATP-hydrolytic action of myocardial Na(+)-K(+)-ATPase depend on the K+ concentration of the incubation medium. These effects seem to be related to the mode by which antiarrhythmic drugs may induce or aggravate cardiac arrhythmias. In addition, the present results suggest that hypokalemia may exacerbate arrhythmias during treatment with these drugs.