Slow delayed rectifier current and repolarization in canine cardiac Purkinje cells.
Although cardiac Purkinje cells (PCs) are believed to be the source of early afterdepolarizations generating ventricular tachyarrhythmias in long Q-T syndromes (LQTS), the ionic determinants of PC repolarization are incompletely known. To evaluate the role of the slow delayed rectifier current (I(Ks)) in PC repolarization, we studied PCs from canine ventricular false tendons with whole cell patch clamp (37 degrees C). Typical I(Ks) voltage- and time-dependent properties were noted. Isoproterenol enhanced I(Ks) in a concentration-dependent fashion (EC(50) approximately 30 nM), negatively shifted I(Ks) activation voltage dependence, and accelerated I(Ks) activation. Block of I(Ks) with 293B did not alter PC action potential duration (APD) in the absence of isoproterenol; however, in the presence of isoproterenol, 293B significantly prolonged APD. We conclude that, without beta-adrenergic stimulation, I(Ks) contributes little to PC repolarization; however, beta-adrenergic stimulation increases the contribution of I(Ks) by increasing current amplitude, accelerating I(Ks) activation, and shifting activation voltage toward the PC plateau voltage range. I(Ks) may therefore provide an important "braking" function to limit PC APD prolongation in the presence of beta-adrenergic stimulation.
Han
W
W
Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec H3G 1Y6, Canada.
Wang
Z
Z
Nattel
S
S
D000081:Acetamides / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001570:Benzodiazepinones / Q000494:pharmacology; D051668:Delayed Rectifier Potassium Channels; D004285:Dogs; D007545:Isoproterenol / Q000494:pharmacology; D008133:Long QT Syndrome / Q000503:physiopathology*; D018408:Patch-Clamp Techniques / Q000592:standards; D015221:Potassium Channels / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D011690:Purkinje Fibers / Q000502:physiology*; D015203:Reproducibility of Results; D017180:Tachycardia, Ventricular / Q000503:physiopathology*; D013710:Tendons
D000081:Acetamides; D000318:Adrenergic beta-Agonists; D000889:Anti-Arrhythmia Agents; D001570:Benzodiazepinones; D051668:Delayed Rectifier Potassium Channels; C109598:L 768673; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D007545:Isoproterenol