L-type Calcium Current (ICa,L) and Inward Rectifier Potassium Current (IK1) are Involved in QT Prolongation Induced by Arsenic Trioxide in Rat

Cellular Physiology and Biochemistry

关键词: As2O3;    QT prolongation;    Rat ventricular cardiomyocytes;    Action potential;    IK1;    ICa;    L;    Intracellular calcium;   

DOI  :  10.1159/000324005

学科分类：分子生物学，细胞生物学和基因

来源: S Karger AG

【 摘 要 】

The present study was designed to study the effects of As₂O₃ on QT interval prolongation and to explore the potential ionic mechanisms in isolated rat ventricular cardiomyocytes. The rats of As₂O₃ group were treated with 0.8 mg·kg^-1·d^-1 As₂O₃ 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. [Ca²⁺]_>i was examined by confocal laser scanning microscopy. Our data showed that both QTc and APD were prolonged significantly after As₂O₃treatment. Meanwhile, As₂O₃ 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 As₂O₃ administration. Furthermore, the maximal [Ca²⁺] _i was enhanced obviously by either KCl or caffeine stimulation in As₂O₃-treated cardiomyocytes. Our results show that the potential mechanism of As₂O₃-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.

【 授权许可】

CC BY-NC-ND