Action Potential Morphology of Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes Does Not Predict Cardiac Chamber Specificity and Is Dependent on Cell Density

• Published in: Biophysical journal Vol. 108; no. 1; pp. 1 - 4
• Main Authors: Du, David T.M., Hellen, Nicola, Kane, Christopher, Terracciano, Cesare M.N.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 06.01.2015; Biophysical Society; The Biophysical Society
• Subjects: Action Potentials - drug effects; Action Potentials - physiology; Biophysical Letter; Carbenoxolone - pharmacology; Cardiomyocytes; Cardiovascular Agents - pharmacology; Cell Count; Cell culture; Cell Culture Techniques; Cells, Cultured; Gap Junctions - drug effects; Gap Junctions - physiology; Genotype & phenotype; Human subjects; Humans; Induced Pluripotent Stem Cells - drug effects; Induced Pluripotent Stem Cells - physiology; Linear Models; Morphology; Myocytes, Cardiac - drug effects; Myocytes, Cardiac - physiology; Optical Imaging; Stem cells; Subpopulations
• ISSN: 0006-3495; 1542-0086; 1542-0086
• DOI: 10.1016/j.bpj.2014.11.008

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.