title: Action potential morphology of human induced pluripotent stem cell-derived cardiomyocytes does not predict cardiac chamber specificity and is dependent on cell density.
abstract: Previous studies investigating human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) have proposed the distinction of heart chamber-specific (atrial, ventricular, pacemaker) electrophysiological phenotypes based on action potential (AP) morphology. This suggestion has been based on data acquired using techniques that allow measurements from only a small number of cells and at low seeding densities. It has also been observed that density of culture affects the properties of iPSC-CMs. Here we systematically analyze AP morphology from iPSC-CMs at two seeding densities: 60,000 cells/well (confluent monolayer) and 15,000 cells/well (sparsely-seeded) using a noninvasive optical method. The confluent cells (n = 360) demonstrate a series of AP morphologies on a normally distributed spectrum with no evidence for specific subpopulations. The AP morphologies of sparsely seeded cells (n = 32) displayed a significantly different distribution, but even in this case there is no clear evidence of chamber-specificity. Reduction in gap junction conductance using carbenoxolone only minimally affected APD distribution in confluent cells. These data suggest that iPSC-CMs possess a sui generis AP morphology, and when observed in different seeding densities may encompass any shape including those resembling chamber-specific subtypes. These results may be explained by different functional maturation due to culture conditions.
authors.affiliation: Myocardial Function Section, National Heart and Lung Institute, Imperial Centre for Translational and Experimental Medicine, Imperial College London, London, United Kingdom.
authors.forename: David T M
authors.initials: DT
authors.lastname: Du
authors.affiliation: Myocardial Function Section, National Heart and Lung Institute, Imperial Centre for Translational and Experimental Medicine, Imperial College London, London, United Kingdom.
authors.forename: Nicola
authors.initials: N
authors.lastname: Hellen
authors.affiliation: Myocardial Function Section, National Heart and Lung Institute, Imperial Centre for Translational and Experimental Medicine, Imperial College London, London, United Kingdom.
authors.forename: Christopher
authors.initials: C
authors.lastname: Kane
authors.affiliation: Myocardial Function Section, National Heart and Lung Institute, Imperial Centre for Translational and Experimental Medicine, Imperial College London, London, United Kingdom. Electronic address: c.terracciano@imperial.ac.uk.
authors.forename: Cesare M N
authors.initials: CM
authors.lastname: Terracciano
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D002229:Carbenoxolone / Q000494:pharmacology; D002317:Cardiovascular Agents / Q000494:pharmacology; D002452:Cell Count; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D017629:Gap Junctions / Q000187:drug effects / Q000502:physiology; D006801:Humans; D057026:Induced Pluripotent Stem Cells / Q000187:drug effects / Q000502:physiology*; D016014:Linear Models; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000502:physiology*; D061848:Optical Imaging
chemical_list: D002317:Cardiovascular Agents; D002229:Carbenoxolone