L-type calcium current (I Ca,L ) and inward rectifier potassium current (I K1 ) 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. Copyright © 2010 S. Karger AG, Basel.