The effect of modifying potassium concentration on the inhibition of myocardial Na(+)-K(+)-ATPase by two class IB antiarrhythmic drugs: lidocaine and tocainide.

1. The inhibitory actions of two class IB antiarrhythmics, lidocaine and tocainide, on Mg(2+)-dependent ATP hydrolysis by myocardial Na(+)-K(+)-ATPase (EC 3.6.1.3), were tested in guinea-pig heart preparations incubated in media containing 2.5, 5.0 and 10 mM K+. 2. The IC50 values for lidocaine were 2.4 +/- 0.4 mM at 2.5, 4.1 +/- 0.8 mM at 5.0 and 5.3 +/- 0.5 mM at 10 mM K+. The corresponding IC20 values were 0.82 +/- 0.12 mM at 2.5, 1.3 +/- 0.2 mM at 5.0 and 1.7 +/- 0.4 mM at 10.0 mM K+ respectively. Tocainide exerted similar action with IC50 values of 3.1 +/- 0.9 mM at 2.5, 7.6 +/- 1.4 mM at 5.0 and 15.5 +/- 1.6 mM at 10.0 mM K+ and IC20 values of 0.71 +/- 0.19 at 2.5, 2.7 +/- 0.5 mM at 5.0 and 12.3 +/- 1.2 mM at 10.0 mM K+ respectively. 3. Thus, the inhibitory potencies of the drugs on myocardial Na(+)-K(+)-ATPase activity increased significantly with reduction in the K+ concentration. These results demonstrate therefore that the inhibitory actions of both lidocaine and tocainide depend on the K+ concentration of the incubation medium. 4. These findings may be indicative of the importance of K+ in some of the cardiac effects of the antiarrhythmic agents, particularly their tendency to induce or enhance already existing cardiac arrhythmias.