title: 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 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.
authors.affiliation: Department of Pharmacology, King Saud University, Riyadh, Saudi Arabia.
authors.forename: A A
authors.initials: AA
authors.lastname: Almotrefi
authors.forename: N
authors.initials: N
authors.lastname: Dzimiri
mesh_terms: D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008012:Lidocaine / Q000494:pharmacology*; D008297:Male; D009206:Myocardium / Q000201:enzymology*; D011188:Potassium / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D016677:Tocainide / Q000494:pharmacology*
chemical_list: D000889:Anti-Arrhythmia Agents; D016677:Tocainide; D008012:Lidocaine; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium