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

Abstract

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 IC 50 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 IC 20 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 IC 50 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 IC 20 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.