Abstract
The electrophysiological effects of carvedilol, a β-blocking agent with vasodilating actions, have been studied on rabbit pacemaker cells using the whole-cell patch clamp technique. Nystatin-perforated patch recordings from the sinoatrial (SA) and atrioventricular (AV) nodes demonstrated that 1-3 μM of carvedilol caused a decrease in the spontaneous firing frequency, depolarization of the maximal diastolic potential, and prolongation of the action potential duration in both species. Voltage clamp experiments were performed using SA and AV node myocytes to identify and define the carvedilol-induced changes in the Ca2+ current, ICa, delayed rectifier K+ current, IK, and hyperpolarization-activated inward current, If. In the SA node cells, 1 μM of carvedilol blocked IK, ICa, and If by 72%, 47%, and 22%, respectively. In the AV node cells, the corresponding reductions were 64% (IK) and 46% (ICa), respectively. In both the SA and AV nodes the decrease in IK appeared to be mainly due to the rapidly activating component of the delayed rectifier, IKr, since the high dose of carvedilol blocked IK in the SA and AV nodes to a submaximal degree. In conclusion, effective doses of carvedilol have classical class III antiarrhythmic actions and a negative chronotropic effect resulting from the inhibition of IK and ICa. Both actions may be efficacious for treating supraventricular tachyarrhythmias. (Int Heart J 2007; 48 : 347-358)
