Abstract
Modulation of intercellular coupling through gap junctions can lead to a decrease in conduction velocity and conduction block. Previous studies have suggested that antiarrhythmic agents alter the internal resistance (sum of cytoplasmic and gap junctions resistances) of cardiac fibers. The objective of this study was to directly assess the effect of antiarrhythmic agents on junctional resistance between two isolated cells using the double whole-cell patch-clamp technique. The experimental protocol consisted in holding the membrane potential of each guinea pig ventricular myocyte of a coupled cell pair at 0 mV. Then, a junctional voltage gradient was created by changing membrane potential in only one cell. Voltage gradients were varied between −50 to +50 mV in steps of 20 mV. The extracellular medium was set to minimize trans-sarcolemmal currents and the junctional current was recorded in the cell maintained at 0 mV. Drugs tested were quinidine, lidocaine, procainamide, flecainide, propranolol, sotalol, amiodarone and verapamil. Drugs were superfused after a control period of 5 min. during which junctional resistance was observed to be stable. None of the antiarrhythmic agents tested in this study directly affected junctional resistance, although procainamide slightly increased junctional resistance 110 ± 8% after 10 min of exposure. In conclusion, drugs tested in this study, chosen among all classes of antiarrhythmic agents, did not affect junctional resistance of cardiac myocyte cell pairs. However, long-term modulation or indirect effects of antiarrhythmic agents on gap junctions under physiological conditions cannot be excluded.
Footnotes
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Send reprint requests to: Pascal Daleau, Ph.D., Quebec Heart Institute, Research Centre, Laval Hospital, 2725 chemin Sainte-Foy, Sainte-Foy, Quebec, Canada G1V 4G5. E-mail:pascal.daleau{at}phc.ulaval.ca
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↵1 This work was supported by grants from the Medical Research Council of Canada (MT12883) and by an operating grant from the Heart & Stroke Foundation of Canada. P.D. received a scholarship from the Fonds de la Recherche en Santé du Québec (950122–103).
- Abbreviations:
- ri
- longitudinal resistance of a unit length of fiber
- rj
- junctional resistance
- rm
- membrane resistance
- Ij
- junctional current
- Im
- membrane current
- Vj
- transjunctional voltage
- λ
- length constant
- θ
- conduction velocity
- Vmax
- maximal rate of depolarization of the action potential
- IK1
- inward rectifier potassium current
- Received August 13, 1997.
- Accepted November 17, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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