title: L-type calcium current (ICa,L) and inward rectifier potassium current (IK1) are involved in QT prolongation induced by arsenic trioxide in rat.
abstract: The present study was designed to study the effects of As(2)O(3) on QT interval prolongation and to explore the potential ionic mechanisms in isolated rat ventricular cardiomyocytes. The rats of As(2)O(3) group were treated with 0.8 mg·kg(-1)·d(-1) As(2)O(3) intravenously for 7 days consecutively and the control group with saline. The ECG was recorded to calculate heart rate-corrected QT interval (QTc). Single cardiomyocytes were isolated by using collagenase II, and the action potential duration (APD) and ion currents were recorded by whole-cell patch clamp. [Ca(2+)](i) was examined by confocal laser scanning microscopy. Our data showed that both QTc and APD were prolonged significantly after As(2)O(3)treatment. Meanwhile, As(2)O(3) suppressed I(K1) and shifted the reversal potential to more positive direction. Moreover, the density of I(Ca,L) was augmented significantly, and the steady-state activation curve became more negative, whereas, the inactivation and reactivation of I(Ca,L) were not changed notably after As(2)O(3) administration. Furthermore, the maximal [Ca(2+)](i) was enhanced obviously by either KCl or caffeine stimulation in As(2)O(3)-treated cardiomyocytes. Our results show that the potential mechanism of As(2)O(3)-induced QT interval prolongation in rat might be relative to disturbing the fine balance of transmembrane currents (increasing I(Ca,L) and decreasing I(K1)) and causing APD prolongation.
authors.affiliation: Institute of Clinical Pharmacy, the Second Affiliated Hospital, Harbin Medical University, Harbin, China.
authors.forename: Xichuang
authors.initials: X
authors.lastname: Chen
authors.forename: Hongli
authors.initials: H
authors.lastname: Shan
authors.forename: Jinlong
authors.initials: J
authors.lastname: Zhao
authors.forename: Yuan
authors.initials: Y
authors.lastname: Hong
authors.forename: Yunlong
authors.initials: Y
authors.lastname: Bai
authors.forename: Iihua
authors.initials: I
authors.lastname: Sun
authors.forename: Zhenwei
authors.initials: Z
authors.lastname: Pan
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Baofeng
authors.initials: B
authors.lastname: Yang
authors.forename: Zhimin
authors.initials: Z
authors.lastname: Du
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D000077237:Arsenic Trioxide; D001152:Arsenicals; D002110:Caffeine / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D004562:Electrocardiography; D006321:Heart / Q000187:drug effects; D008297:Male; D018613:Microscopy, Confocal; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D010087:Oxides / Q000633:toxicity*; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000502:physiology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000970:Antineoplastic Agents; D001152:Arsenicals; D020746:Calcium Channels, L-Type; D010087:Oxides; D024661:Potassium Channels, Inwardly Rectifying; D002110:Caffeine; D011189:Potassium Chloride; D000077237:Arsenic Trioxide