Electrophysiological effects of carvedilol on rabbit heart pacemaker cells.
The electrophysiological effects of carvedilol, a beta-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 microM 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 Ca(2+) current, I(Ca), delayed rectifier K(+) current, I(K), and hyperpolarization-activated inward current, I(f). In the SA node cells, 1 microM of carvedilol blocked I(K), I(Ca), and I(f) by 72%, 47%, and 22%, respectively. In the AV node cells, the corresponding reductions were 64% (I(K)) and 46% (I(Ca)), respectively. In both the SA and AV nodes the decrease in I(K) appeared to be mainly due to the rapidly activating component of the delayed rectifier, I(Kr), since the high dose of carvedilol blocked I(K) 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 I(K) and I(Ca). Both actions may be efficacious for treating supraventricular tachyarrhythmias.
Yokoyama
Ayumi
A
First Department of Internal Medicine, Asahikawa Medical College, Hokkaido.
Sato
Nobuyuki
N
Kawamura
Yuichiro
Y
Hasebe
Naoyuki
N
Kikuchi
Kenjiro
K
D000200:Action Potentials / Q000187:drug effects; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D001283:Atrioventricular Node / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000378:metabolism; D002227:Carbazoles / Q000494:pharmacology*; D002304:Cardiac Pacing, Artificial / Q000379:methods*; D000077261:Carvedilol; D004195:Disease Models, Animal; D018408:Patch-Clamp Techniques / Q000379:methods; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011412:Propanolamines / Q000494:pharmacology*; D011817:Rabbits; D012849:Sinoatrial Node / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D013617:Tachycardia, Supraventricular / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
D000319:Adrenergic beta-Antagonists; D020746:Calcium Channels, L-Type; D002227:Carbazoles; D015221:Potassium Channels; D011412:Propanolamines; D000077261:Carvedilol