Electrophysiological consequences of human IKs channel expression in adult murine heart.
We expressed human delayed rectifier K(+) cardiac current (I(Ks)) channels in the murine heart, which lacks native I(Ks), to determine their electrophysiological role. Mice expressing human I(Ks) channels were anesthetized, and an electrocardiogram and monophasic action potentials (MAP) recorded from the left ventricle. Sinus rate was not different between wild-type mice (WT) and transgenic mice (TG). Infusion of isoproterenol accelerated WT heart rate but not TG. Lack of TG sinus rate responsiveness may have resulted from accumulated outward current in I(Ks) channels in sinus node. Ventricular MAP duration of TG mice to 50% repolarization (APD(50)) during ventricular pacing was shorter than WT, likely resulting from outward current through I(Ks) channels. TG APD(50) showed enhanced responsiveness (shortening) to isoproterenol compared with WT. Ventricular tachyarrhythmias were initiated in TG mice by programmed stimulation but not in WT and were accelerated by isoproterenol. I(Ks) channels impart beta-adrenergic sensitivity to the ventricles and may be responsible for ventricular tachyarrhythmias.
Chiello Tracy
Christine
C
Department of Pharmacology, Columbia University, College of Physicians and Surgeons, New York, New York 10032, USA.
Cabo
Candido
C
Coromilas
James
J
Kurokawa
Junko
J
Kass
Robert S
RS
Wit
Andrew L
AL
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D051668:Delayed Rectifier Potassium Channels; D004594:Electrophysiology; D005260:Female; D006339:Heart Rate; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics; D009206:Myocardium / Q000378:metabolism*; D015221:Potassium Channels / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000503:physiopathology; D016276:Ventricular Function / Q000187:drug effects
D000318:Adrenergic beta-Agonists; D051668:Delayed Rectifier Potassium Channels; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D007545:Isoproterenol