title: Automated patch clamp on mESC-derived cardiomyocytes for cardiotoxicity prediction.
abstract: Cardiovascular side effects are critical in drug development and have frequently led to late-stage project terminations or even drug withdrawal from the market. Physiologically relevant and predictive assays for cardiotoxicity are hence strongly demanded by the pharmaceutical industry. To identify a potential impact of test compounds on ventricular repolarization, typically a variety of ion channels in diverse heterologously expressing cells have to be investigated. Similar to primary cells, in vitro-generated stem cell-derived cardiomyocytes simultaneously express cardiac ion channels. Thus, they more accurately represent the native situation compared with cell lines overexpressing only a single type of ion channel. The aim of this study was to determine if stem cell-derived cardiomyocytes are suited for use in an automated patch clamp system. The authors show recordings of cardiac ion currents as well as action potential recordings in readily available stem cell-derived cardiomyocytes. Besides monitoring inhibitory effects of reference compounds on typical cardiac ion currents, the authors revealed for the first time drug-induced modulation of cardiac action potentials in an automated patch clamp system. The combination of an in vitro cardiac cell model with higher throughput patch clamp screening technology allows for a cost-effective cardiotoxicity prediction in a physiologically relevant cell system.
authors.affiliation: Nanion Technologies GmbH, Gabrielenstrasse 9, Munich, Germany. sonja@nanion.de
authors.forename: Sonja
authors.initials: S
authors.lastname: Stoelzle
authors.forename: Alison
authors.initials: A
authors.lastname: Haythornthwaite
authors.forename: Ralf
authors.initials: R
authors.lastname: Kettenhofen
authors.forename: Eugen
authors.initials: E
authors.lastname: Kolossov
authors.forename: Heribert
authors.initials: H
authors.lastname: Bohlen
authors.forename: Michael
authors.initials: M
authors.lastname: George
authors.forename: Andrea
authors.initials: A
authors.lastname: Brüggemann
authors.forename: Niels
authors.initials: N
authors.lastname: Fertig
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D057205:Automation, Laboratory; D001688:Biological Products / Q000009:adverse effects* / Q000494:pharmacology; D002454:Cell Differentiation; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions / Q000378:metabolism*; D006321:Heart / Q000187:drug effects*; D057166:High-Throughput Screening Assays; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism
chemical_list: D001688:Biological Products; D007473:Ion Channels