Cellular electropharmacology of human atrium: effects of antiarrhythmic drugs

Human atrial tissue exhibits specific electrophysiological properties such as the presence of plateau shaped action potentials characterized by an initial notch followed by a long lasting plateau. In these cells, the notch and the plateau are due to the activation of transient outward currents Ito and slow inward current Isi. The effects of antiarrhythmic agents on this tissue depend on the morphology of the action potentials. We demonstrated that, in these plateau shaped fibers, action potential duration at 50 and 90% of repolarization was increased by flecainide at the concentration of 5 x 10(-7)M. This increase is due to the effect of the drug on Ito, as shown by experiments with 4 amino-pyridine, a blocker of transient outward currents. We also demonstrated that quinidine at the concentration of 10(-5)M decreased in these cells the action potential duration at 50% of repolarization. This decrease is due to the effects of the drug on Isi, as confirmed by experiments using the patch-clamp technique. These modifications of the repolarization duration were not obtained in triangular action potentials which are observed in young subjects and in patients with chronic atrial fibrillation. In these triangular action potentials both Ito and Isi are inactivated. Since the animal tissues do not exhibit the same electrophysiological inhomogeneity, it is interesting to test the different classes of antiarrhythmic drugs on human atrium. These studies on human tissue, especially on diseased atrium, are closer to clinical situations than those performed on normal animal tissue.