{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T16:14:55Z","timestamp":1778861695085,"version":"3.51.4"},"reference-count":33,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T00:00:00Z","timestamp":1715731200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["U01HL136297"],"award-info":[{"award-number":["U01HL136297"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["F31HL154655"],"award-info":[{"award-number":["F31HL154655"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2024,10]]},"abstract":"\n Abstract<\/jats:title>\n \n All new drugs must go through preclinical screening tests to determine their proarrhythmic potential. While these assays effectively filter out dangerous drugs, they are too conservative, often misclassifying safe compounds as proarrhythmic. In this study, we attempt to address this shortcoming with a novel, medium\u2010throughput drug\u2010screening approach: we use an automated patch\u2010clamp system to acquire optimized voltage clamp (VC) and action potential (AP) data from human induced pluripotent stem cell\u2010derived cardiomyocytes (iPSC\u2010CMs) at several drug concentrations (baseline, 3\u00d7, 10\u00d7 and 20\u00d7 the effective free plasma concentrations). With our novel method, we show correlations between\n I<\/jats:italic>\n Na<\/jats:sub>\n block and upstroke slowing after treatment with flecainide or quinine. Additionally, after quinine treatment, we identify significant reductions in current during voltage steps designed to isolate\n I<\/jats:italic>\n f<\/jats:sub>\n and\n I<\/jats:italic>\n Ks<\/jats:sub>\n . However, we do not detect any\n I<\/jats:italic>\n Kr<\/jats:sub>\n block by either drug, and upon further investigation, do not see any\n I<\/jats:italic>\n Kr<\/jats:sub>\n present in the iPSC\u2010CMs when prepared for automated patch experiments (i.e. in suspension) \u2013 this is in contrast to similar experiments we have conducted with these cells using the manual patch setup. In this study, we: (1) present a proof\u2010of\u2010concept demonstration of a single\u2010cell medium\u2010throughput drug study, and (2) characterize the non\u2010canonical electrophysiology of iPSC\u2010CMs when prepared for experiments in a medium\u2010throughput setting.\n \n \n image<\/jats:alt-text>\n <\/jats:graphic>\n <\/jats:boxed-text>\n <\/jats:p>\n <\/jats:sec>\n \n Key points<\/jats:title>\n \n \n \n \n Human induced pluripotent stem cell\u2010derived cardiomyocytes (iPSC\u2010CMs) offer potential as an\n in vitro<\/jats:italic>\n model to study the proarrhythmic potential of drugs, but insights from these cells are often limited by the low throughput of manual patch\u2010clamp.\n <\/jats:p>\n <\/jats:list-item>\n \n In this study, we use a medium\u2010throughput automated patch\u2010clamp system to acquire action potential (AP) and complex voltage clamp (VC) data from single iPSC\u2010CMs at multiple drug concentrations.<\/jats:p>\n <\/jats:list-item>\n \n \n A correlation between AP upstroke and\n I<\/jats:italic>\n Na<\/jats:sub>\n transients was identified and drug\u2010induced changes in ionic currents found.\n <\/jats:p>\n <\/jats:list-item>\n \n We also characterize the substantially altered physiology of iPSC\u2010CMs when patched in an automated system, suggesting the need to investigate differences between manual and automated patch experiments.<\/jats:p>\n <\/jats:list-item>\n <\/jats:list>\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1113\/jp285120","type":"journal-article","created":{"date-parts":[[2024,5,15]],"date-time":"2024-05-15T04:12:08Z","timestamp":1715746328000},"page":"5163-5178","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Single\u2010cell ionic current phenotyping elucidates non\u2010canonical features and predictive potential of cardiomyocytes during automated drug experiments"],"prefix":"10.1113","volume":"602","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5200-6573","authenticated-orcid":false,"given":"Alexander P.","family":"Clark","sequence":"first","affiliation":[{"name":"Department of Biomedical Engineering Cornell University Ithaca New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1085-6788","authenticated-orcid":false,"given":"Siyu","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology SUNY Downstate Health Sciences University Brooklyn New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0852-2922","authenticated-orcid":false,"given":"David J.","family":"Christini","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering Cornell University Ithaca New York USA"},{"name":"Department of Physiology and Pharmacology SUNY Downstate Health Sciences 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