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Novel antiarrhythmic therapies are required to overcome current drug limitations related to effectiveness and pro-arrhythmia risk in some contexts. Cardiomyocyte culture models provide a high-throughput platform for screening antiarrhythmic compounds, but comparative information about electrophysiological properties of commonly used types of cardiomyocyte preparations is lacking. Standardization of cultured cardiomyocyte microelectrode array (MEA) experimentation is required for its application as a high-throughput platform for antiarrhythmic drug development. The aim of this study was to directly compare the electrophysiological properties and responses to isoproterenol of three commonly used cardiac cultures. Neonatal rat ventricular myocytes (NRVMs), immortalized atrial HL-1 cells, and custom-generated human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were cultured on microelectrode arrays for 48\u2013120 h. Extracellular field potentials were recorded, and conduction velocity was mapped in the presence\/absence of the \u03b2-adrenoceptor agonist isoproterenol (1 \u00b5M). Field potential amplitude and conduction velocity were greatest in NRVMs and did not differ in cardiomyocytes isolated from male\/female hearts. Both NRVMs and hiPSC-CMs exhibited longer field potential durations with rate dependence and were responsive to isoproterenol. In contrast, HL-1 cells exhibited slower conduction and shorter field potential durations and did not respond to 1 \u00b5M isoproterenol. This is the first study to compare the intrinsic electrophysiologic properties of cultured cardiomyocyte preparations commonly used for in vitro electrophysiology assessment. These findings offer important comparative data to inform methodological approaches in the use of MEA and other techniques relating to cardiomyocyte functional screening investigations of particular relevance to arrhythmogenesis. <\/jats:p>","DOI":"10.1152\/ajpcell.00306.2019","type":"journal-article","created":{"date-parts":[[2019,10,2]],"date-time":"2019-10-02T19:07:05Z","timestamp":1570043225000},"page":"C1256-C1267","source":"Crossref","is-referenced-by-count":30,"title":["Cardiomyocyte functional screening: interrogating comparative electrophysiology of high-throughput model cell systems"],"prefix":"10.1152","volume":"317","author":[{"given":"Simon P.","family":"Wells","sequence":"first","affiliation":[{"name":"Department of Physiology, School of Biomedical Sciences, University of Melbourne, Melbourne, Victoria, Australia"},{"name":"Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen M.","family":"Waddell","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Biomedical Sciences, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Choon Boon","family":"Sim","sequence":"additional","affiliation":[{"name":"Murdoch Children\u2019s Research Institute, Royal Children\u2019s Hospital, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0442-3655","authenticated-orcid":false,"given":"Shiang Y.","family":"Lim","sequence":"additional","affiliation":[{"name":"St. Vincent\u2019s Institute of Medical Research, Fitzroy, Victoria, Australia"},{"name":"Departments of Medicine and Surgery, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriel B.","family":"Bernasochi","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Biomedical Sciences, University of Melbourne, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3171-3551","authenticated-orcid":false,"given":"Davor","family":"Pavlovic","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paulus","family":"Kirchhof","sequence":"additional","affiliation":[{"name":"Institute of Cardiovascular Sciences, College of Medical and Dental Sciences, University of Birmingham, United Kingdom"},{"name":"Departments of Cardiology, University Hospitals Birmingham and Sandwell and West Birmingham Hospitals National Health Service Trusts, Birmingham, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enzo R.","family":"Porrello","sequence":"additional","affiliation":[{"name":"Department of Physiology, School of Biomedical Sciences, University of Melbourne, Melbourne, Victoria, Australia"},{"name":"Murdoch Children\u2019s Research Institute, Royal Children\u2019s Hospital, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea M. 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