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Single-Cell Optical Action Potential Measurement in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes
Published on: December 22, 2020
Drug Testing in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes From a Patient With Short QT Syndrome Type
Zhihan Zhao1,2,3, Xin Li1, Ibrahim El-Battrawy1,2
1First Department of Medicine, Medical Faculty Mannheim, University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany.
Abstract:
Short QT syndrome (SQTS) predisposes afflicted patients to sudden cardiac death. Until now, only one drug-quinidine-has been shown to be effective in patients with SQTS type 1(SQTS1). The objective of this study was to use human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a patient with SQTS1 to search for potentially effective drugs for the treatment of SQTS1 patients. Patch clamp and single-cell contraction measurements were employed to assess drug effects. Ivabradine, mexiletine, and ajmaline but not flecainide, ranolazine, or amiodarone prolonged the action potential duration (APD) in hiPSC-CMs from an SQTS1 patient. Ivabradine, ajmaline, and mexiletine inhibited KCNH2 channel currents significantly, which may underlie their APD-prolonging effects. Under proarrhythmic epinephrine stimulation in spontaneously beating SQTS1 hiPSC-CMs, ivabradine, mexiletine, and ajmaline but not flecainide reduced the epinephrine-induced arrhythmic events. The results demonstrate that ivabradine, ajmaline, and mexiletine may be candidate drugs for preventing tachyarrhythmias in SQTS1 patients.
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