Action Potential Characterization of Human Induced Pluripotent Stem Cell–Derived Cardiomyocytes Using Automated Patch-Clamp Technology

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