{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,17]],"date-time":"2026-02-17T02:56:38Z","timestamp":1771296998409,"version":"3.50.1"},"reference-count":57,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2015,10,15]],"date-time":"2015-10-15T00:00:00Z","timestamp":1444867200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec><jats:title>Background and Purpose<\/jats:title><jats:p>Two new technologies are likely to revolutionize cardiac safety and drug development: <jats:italic>in vitro<\/jats:italic> experiments on human\u2010induced pluripotent stem cell\u2010derived cardiomyocytes (hiPSC\u2010CMs) and <jats:italic>in silico<\/jats:italic> human adult ventricular cardiomyocyte (hAdultV\u2010CM) models. Their combination was recently proposed as a potential replacement for the present hERG\u2010based QT study for pharmacological safety assessments. Here, we systematically compared <jats:italic>in silico<\/jats:italic> the effects of selective ionic current block on hiPSC\u2010CM and hAdultV\u2010CM action potentials (APs), to identify similarities\/differences and to illustrate the potential of computational models as supportive tools for evaluating new <jats:italic>in vitro<\/jats:italic> technologies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Experimental Approach<\/jats:title><jats:p><jats:italic>In silico<\/jats:italic> AP models of ventricular\u2010like and atrial\u2010like hiPSC\u2010CMs and hAdultV\u2010CM were used to simulate the main effects of four degrees of block of the main cardiac transmembrane currents.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Qualitatively, hiPSC\u2010CM and hAdultV\u2010CM APs showed similar responses to current block, consistent with results from experiments. However, quantitatively, hiPSC\u2010CMs were more sensitive to block of (i) L\u2010type Ca<jats:sup>2+<\/jats:sup> currents due to the overexpression of the Na<jats:sup>+<\/jats:sup>\/Ca<jats:sup>2+<\/jats:sup> exchanger (leading to shorter APs) and (ii) the inward rectifier K<jats:sup>+<\/jats:sup> current due to reduced repolarization reserve (inducing diastolic potential depolarization and repolarization failure).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions and Implications<\/jats:title><jats:p><jats:italic>In silico<\/jats:italic> hiPSC\u2010CMs and hAdultV\u2010CMs exhibit a similar response to selective current blocks. However, overall hiPSC\u2010CMs show greater sensitivity to block, which may facilitate <jats:italic>in vitro<\/jats:italic> identification of drug\u2010induced effects. Extrapolation of drug effects from hiPSC\u2010CM to hAdultV\u2010CM and pro\u2010arrhythmic risk assessment can be facilitated by <jats:italic>in silico<\/jats:italic> predictions using biophysically\u2010based computational models.<\/jats:p><\/jats:sec>","DOI":"10.1111\/bph.13282","type":"journal-article","created":{"date-parts":[[2015,8,15]],"date-time":"2015-08-15T13:53:00Z","timestamp":1439646780000},"page":"5147-5160","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":63,"title":["Human induced pluripotent stem cell\u2010derived versus adult cardiomyocytes: an <i>in silico<\/i> electrophysiological study on effects of ionic current block"],"prefix":"10.1111","volume":"172","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0510-1444","authenticated-orcid":false,"given":"M","family":"Paci","sequence":"first","affiliation":[{"name":"Department of Electronics and Communications Engineering Tampere University of Technology, 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