Electrophysiological effects of ibutilide on the delayed rectifier K(+) current in rabbit sinoatrial and atrioventricular node cells.
Biophysical and pharmacological characteristics of the delayed rectifier K(+) current (I(K)) of rabbit sinoatrial (SA) node and atrioventricular (AV) node cells have been studied using the whole-cell patch clamp technique together with a recently developed antiarrhythmic agent, ibutilide. Ibutilide is a potent blocker of the rapid delayed rectifier K(+) current, I(Kr). Superfusion with ibutilide (10(-7) M) caused a decrease in the spontaneous firing frequency, depolarization of the maximal diastolic potential and prolongation of the action potential duration in both SA and AV node cells. In whole cell voltage clamp experiments done on myocytes from SA node, ibutilide (10(-7) M) blocked I(K) strongly (40%) and had smaller effects on Ca(2+) current (10%) and hyperpolarization-activated inward current, I(f) (11%). In AV node cells, the corresponding reductions were I(K) (68%), I(Ca) (13%) and I(f) (10%), respectively. A 10-fold increase in the concentration of ibutilide further decreased I(K) in SA node cells (67+/-8%), and blocked I(K) almost completely in AV node cells. These results are consistent with the hypothesis that the delayed rectifier K(+) current in SA node cell is generated by both I(Kr) and I(Ks), whereas I(Kr) predominates in AV node cells. Knowledge of the differences in the distribution of I(Kr), as well as the different sensitivity to blockers of I(Kr) in nodal cells, is important for understanding modifications of the automaticity, conduction velocity, and refractoriness by class III antiarrhythmic agents.
Sato
N
N
Department of Physiology and Biophysics, The University of Calgary, Calgary, Alberta, Canada. nsato@asahikawa-med.ac.jp
Tanaka
H
H
Habuchi
Y
Y
Giles
W R
WR
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001283:Atrioventricular Node / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D024642:Potassium Channels, Voltage-Gated; D011817:Rabbits; D012849:Sinoatrial Node / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology*
D000889:Anti-Arrhythmia Agents; D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D013449:Sulfonamides; C067192:ibutilide