Electrophysiological consequences of humanI Ks channel expression in adult murine heart

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Abstract
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 Kschannels in sinus node. Ventricular MAP duration of TG mice to 50% repolarization (APD50) during ventricular pacing was shorter than WT, likely resulting from outward current through I Ks channels. TG APD50 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 β-adrenergic sensitivity to the ventricles and may be responsible for ventricular tachyarrhythmias.