Application of optical action potentials in human induced pluripotent stem cells-derived cardiomyocytes to predict drug-induced cardiac arrhythmias

Journal of Pharmacological and Toxicological Methods
H R LuG Smith

Abstract

Human induced pluripotent stem cell-derived cardiomyocytes (hiPS-CMs) are emerging as new and human-relevant source in vitro model for cardiac safety assessment that allow us to investigate a set of 20 reference drugs for predicting cardiac arrhythmogenic liability using optical action potential (oAP) assay. Here, we describe our examination of the oAP measurement using a voltage sensitive dye (Di-4-ANEPPS) to predict adverse compound effects using hiPS-CMs and 20 cardioactive reference compounds. Fluorescence signals were digitized at 10kHz and the records subsequently analyzed off-line. Cells were exposed to 30min incubation to vehicle or compound (n=5/dose, 4 doses/compound) that were blinded to the investigating laboratory. Action potential parameters were measured, including rise time (Trise) of the optical action potential duration (oAPD). Significant effects on oAPD were sensitively detected with 11 QT-prolonging drugs, while oAPD shortening was observed with ICa-antagonists, IKr-activator or ATP-sensitive K(+) channel (KATP)-opener. Additionally, the assay detected varied effects induced by 6 different sodium channel blockers. The detection threshold for these drug effects was at or below the published values of free ef...Continue Reading

References

Apr 1, 1984·Journal of Clinical Pharmacology·E M Vaughan Williams

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Citations

Oct 27, 2018·Toxicological Sciences : an Official Journal of the Society of Toxicology·Haoyu ZengFrederick Sannajust
Mar 7, 2018·NPJ Systems Biology and Applications·Jingqi Q X Gong, Eric A Sobie
Apr 26, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Hua Rong LuDavid J Gallacher
Mar 27, 2019·Toxicological Sciences : an Official Journal of the Society of Toxicology·Dakshesh PatelKsenia Blinova
Jun 25, 2020·Journal of Pharmacological and Toxicological Methods·Stéphane BedutJean-Marc D'Angelo
Sep 3, 2019·Progress in Biophysics and Molecular Biology·Corey D AckerLeslie M Loew
Jul 3, 2021·International Journal of Molecular Sciences·Ana Da Silva CostaGodfrey L Smith
Jul 28, 2021·Europace : European Pacing, Arrhythmias, and Cardiac Electrophysiology : Journal of the Working Groups on Cardiac Pacing, Arrhythmias, and Cardiac Cellular Electrophysiology of the European Society of Cardiology·Katja E OdeningJordi Heijman
Feb 9, 2019·ACS Chemical Biology·Steven C BoggessEvan W Miller

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