scholarly journals Characterization of the Halothane-Anesthetized Guinea-Pig Heart as a Model to Detect the K+ Channel Blocker-Induced QT-Interval Prolongation

2006 ◽  
Vol 29 (4) ◽  
pp. 827-829 ◽  
Author(s):  
Akira Takahara ◽  
Atsushi Sugiyama ◽  
Keitaro Hashimoto
Keyword(s):  
Guinea Pig ◽  
Qt Interval ◽  
Channel Blocker ◽  
K Channel ◽  
Interval Prolongation ◽  
Guinea Pig Heart ◽  
Qt Interval Prolongation

scholarly journals QT PRODACT: Evaluation of the Potential of Compounds to Cause QT Interval Prolongation by Action Potential Assays Using Guinea-Pig Papillary Muscles

2005 ◽  
Vol 99 (5) ◽  
pp. 449-457 ◽  
Author(s):  
Yoshihide Kii ◽  
Seiji Hayashi ◽  
Mitsuyasu Tabo ◽  
Takashi Shimosato ◽  
Hitoshi Fukuda ◽  
...  
Keyword(s):  
Guinea Pig ◽  
Action Potential ◽  
Qt Interval ◽  
Papillary Muscles ◽  
Interval Prolongation ◽  
Qt Interval Prolongation

scholarly journals Ginsenoside Rg3 Alleviates Antithyroid Cancer Drug Vandetanib-Induced QT Interval Prolongation

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Juan Zhang ◽  
Dan Luo ◽  
Fang Li ◽  
Zhiyi Li ◽  
Xiaoli Gao ◽  
...  
Keyword(s):  
Patch Clamp ◽  
Action Potential ◽  
Cardiac Arrhythmia ◽  
Qt Interval ◽  
K Channel ◽  
Ginsenoside Rg3 ◽  
Interval Prolongation ◽  
Patch Clamp Technique ◽  
Clamp Technique ◽  
Qt Interval Prolongation

Inhibition of human ether-a-go-go-related gene (hERG) potassium channel is responsible for acquired long QT syndromes, which leads to life-threatening cardiac arrhythmia. A multikinase inhibitor, vandetanib, prolongs the progression-free survival time in advanced medullary thyroid cancer. However, vandetanib has been reported to induce significant QT interval prolongation, which limits its clinical application. Some studies have showed that ginsenoside Rg3 decelerated hERG K(+) channel tail current deactivation. Therefore, in this study, we aim to confirm whether ginsenoside Rg3 targeting hERG K(+) channel could be used to reverse the vandetanib-induced QT interval prolongation. Electrocardiogram (ECG) and monophasic action potential (MAP) were recorded using electrophysiology signal sampling and analysis system in Langendorff-perfused rabbit hearts. The current clamp mode of the patch-clamp technique was used to record transmembrane action potential. The whole-cell patch-clamp technique was used to record the hERG K+ current. In Langendorff-perfused hearts, vandetanib prolonged the QT interval in a concentration-dependent manner with an IC50 of 1.96 μmol/L. In human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs), vandetanib significantly prolonged the action potential duration at 50%, 70%, and 90% repolarization (APD50, APD70, and APD90). In stable transfected human hERG gene HEK293 cells, vandetanib caused concentrate-dependent inhibition in the step and tail currents of hERG. As expected, ginsenoside Rg3 relieved vandetanib-induced QT interval prolongation in Langendorff-perfused heart and reversed vandetanib-induced APD prolongation in hiPSC-CMs. Furthermore, ginsenoside Rg3 alleviated vandetanib-induced hERG current inhibition and accelerated the process of the channel activation. Ginsenoside Rg3 may be a promising cardioprotective agent against vandetanib-induced QT interval prolongation through targeting hERG channel. These novel findings highlight the therapeutic potential of ginsenoside to prevent vandetanib-induced cardiac arrhythmia.

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