EFFECTS OF ANTIARRHYTHMIC AGENTS ON JUNCTIONAL RESISTANCE OF GUINEA-PIG VENTRICULAR CELL PAIRS

Modulation of intercellular coupling through gap junctions can lead to a decrease in conduction velocity and conduction block. Previous stud ies have suggested that antiarrhythmic agents alter the internal resis tance (sum of cytoplasmic and gap junctions resistances) of cardiac fi bers. The objective of this study was to directly assess the effect of antiarrhythmic agents on junctional resistance between two isolated c ells using the double whole-cell patch-clamp technique. The experiment al protocol consisted in holding the membrane potential of each guinea pig ventricular myocyte of a coupled cell pair at 0 mV. Then, a junct ional voltage gradient was created by changing membrane potential in o nly one cell. Voltage gradients were varied between -50 to +50 mV in s teps of 20 mV. The extracellular medium was set to minimize trans-sarc olemmal currents and the junctional current was recorded in the cell m aintained at 0 mV. Drugs tested were quinidine, lidocaine, procainamid e, flecainide, propranolol, sotalol, amiodarone and verapamil. Drugs w ere superfused after a control period of 5 min. during which junctiona l resistance was observed to be stable. None of the antiarrhythmic age nts tested in this study directly affected junctional resistance, alth ough procainamide slightly increased junctional resistance 110 +/- 8% after 10 min of exposure. In conclusion, drugs tested in this study, c hosen among all classes of antiarrhythmic agents, did not affect junct ional resistance of cardiac myocyte cell pairs. However, long-term mod ulation or indirect effects of antiarrhythmic agents on gap junctions under physiological conditions cannot be excluded.