Enhancing effects of salicylate on tonic and phasic block of Na+ channels by class 1 antiarrhythmic agents in the ventricular myocytes and the guinea pig papillary muscle.
OBJECTIVE
To study the interaction between salicylate and class 1 antiarrhythmic agents.


METHODS
The effects of salicylate on class 1 antiarrhythmic agent-induced tonic and phasic block of the Na+ current (INa) of ventricular myocytes and the upstroke velocity of the action potential (Vmax) of papillary muscles were examined by both the patch clamp technique and conventional microelectrode techniques.


RESULTS
Salicylate enhanced quinidine-induced tonic and phasic block of INa at a holding potential of -100 mV but not at a holding potential of -140 mV; this enhancement was accompanied by a shift of the hinfinity curve in the presence of quinidine in a further hyperpolarized direction, although salicylate alone did not affect INa. Salicylate enhanced the tonic and phasic block of Vmax induced by quinidine, aprindine and disopyramide but had little effect on that induced by procainamide or mexiletine; the enhancing effects were related to the liposolubility of the drugs.


CONCLUSIONS
Salicylate enhanced tonic and phasic block of Na+ channels induced by class 1 highly liposoluble antiarrhythmic agents. Based on the modulated receptor hypothesis, it is probable that this enhancement was mediated by an increase in the affinity of Na+ channel blockers with high lipid solubility to the inactivated state channels.
D000200:Action Potentials; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D004357:Drug Synergism; D006168:Guinea Pigs; D006352:Heart Ventricles / Q000187:drug effects*; D008839:Microelectrodes; D010210:Papillary Muscles / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D011802:Quinidine / Q000494:pharmacology; D012459:Salicylates / Q000494:pharmacology*; D026941:Sodium Channel Blockers