| Sign In to gain access to subscriptions and/or personal tools. |
Cellular Mechanism of the QT Prolongation Induced by SulpirideFrom the Department of Pharmacology, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology. Correspondence: Please address correspondence to Eun-Joo Kim, PhD, Department of pharmacology, Korea Institute of Toxicology, Korea Research Institute of Chemical Technology, Yuseong, Daejeon, 305-343, Korea; e-mail:ejkim{at}kitox.re.kr. In this study, the authors investigated the electrophysiological effect of sulpiride on cardiac repolarization using conventional microelectrode recording techniques in isolated canine Purkinje fibers and a whole-cell patch clamp technique in transiently transfected cells with the hERG, KCNQ1/KCNE1, KCNJ2, and SCN5A cDNA and in rat cardiac myocytes for ICa. In studies of action potential duration, 10 µM, 100 µM, 300 µM, and 1 mM sulpiride prolonged action potential duration in a concentration-dependent manner. In studies of cardiac ion channels, sulpiride did not significantly affect INa, ICa, IKs, IK1, except for IKr. Sulpiride dose-dependently decreased the hERG tail current. It is considered that the prolonged action potential duration by sulpiride was mainly the result of inhibition of the hERG channel. The data suggest that the clinical use of sulpiride is reasonable within therapeutic plasma concentrations, but all patients taking this drug should be cautiously monitored for clinical signs of long-QT syndrome and severe arrhythmia.
Key Words: sulpiride • action potential • hERG K+ channel • QT interval prolongation
International Journal of Toxicology, Vol. 28, No. 3,
207-212 (2009) |
||||
 |
|
|
 |
|
Sign In to gain access to subscriptions and/or personal tools.
