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  Action potential characterization of human induced pluripotent stem cell-derived cardiomyocytes using automated patch-clamp technology.

Scheel, O., Frech, S., Amuzescu, B., Eisfeld, J., Lin, K. H., & Knott, T. (2014). Action potential characterization of human induced pluripotent stem cell-derived cardiomyocytes using automated patch-clamp technology. Assay and Drug Development Technologies, 12(8), 457-469. doi:10.1089/adt.2014.601.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0024-4A9D-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002A-0F28-B
Genre: Journal Article

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Scheel, O., Author
Frech, S., Author
Amuzescu, B., Author
Eisfeld, J., Author
Lin, K. H.1, Author              
Knott, T., Author
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1Research Group of Activity-Dependent and Developmental Plasticity at the Calyx of Held, MPI for biophysical chemistry, Max Planck Society, ou_578581              

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 Abstract: Abstract Recent progress in embryonic stem cell (ESC) and induced pluripotent stem cell (iPSC) research led to high-purity preparations of human cardiomyocytes (CMs) differentiated from these two sources-suitable for tissue regeneration, in vitro models of disease, and cardiac safety pharmacology screening. We performed a detailed characterization of the effects of nifedipine, cisapride, and tetrodotoxin (TTX) on Cor.4U(®) human iPSC-CM, using automated whole-cell patch-clamp recordings with the CytoPatch(™) 2 equipment, within a complex assay combining multiple voltage-clamp and current-clamp protocols in a well-defined sequence, and quantitative analysis of several action potential (AP) parameters. We retrieved three electrical phenotypes based on AP shape: ventricular, atrial/nodal, and S-type (with ventricular-like depolarization and lack of plateau). To suppress spontaneous firing, present in many cells, we injected continuously faint hyperpolarizing currents of -10 or -20 pA. We defined quality criteria (both seal and membrane resistance over 1 GΩ), and focused our study on cells with ventricular-like AP. Nifedipine induced marked decreases in AP duration (APD): APD90 (49.8% and 40.8% of control values at 1 and 10 μM, respectively), APD50 (16.1% and 12%); cisapride 0.1 μM increased APD90 to 176.2%; and tetrodotoxin 10 μM decreased maximum slope of phase to 33.3% of control, peak depolarization potential to 76.3% of control, and shortened APD90 on average to 80.4%. These results prove feasibility of automated voltage- and current-clamp recordings on human iPSC-CM and their potential use for in-depth drug evaluation and proarrhythmic liability assessment, as well as for diagnosis and pharmacology tests for cardiac channelopathy patients.

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Language(s): eng - English
 Dates: 2014-10-292014-11-10
 Publication Status: Published in print
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 Rev. Method: Peer
 Identifiers: DOI: 10.1089/adt.2014.601
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Title: Assay and Drug Development Technologies
Source Genre: Journal
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Pages: - Volume / Issue: 12 (8) Sequence Number: - Start / End Page: 457 - 469 Identifier: -