Institut für Herz- und Kreislaufphysiologie

[["dc.bibliographiccitation.firstpage","1765"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Nature Communications"],["dc.bibliographiccitation.volume","13"],["dc.contributor.author","Wagdi, Ahmed"],["dc.contributor.author","Malan, Daniela"],["dc.contributor.author","Sathyanarayanan, Udhayabhaskar"],["dc.contributor.author","Beauchamp, Janosch S."],["dc.contributor.author","Vogt, Markus"],["dc.contributor.author","Zipf, David"],["dc.contributor.author","Beiert, Thomas"],["dc.contributor.author","Mansuroglu, Berivan"],["dc.contributor.author","Dusend, Vanessa"],["dc.contributor.author","Meininghaus, Mark"],["dc.contributor.author","Schneider, Linn"],["dc.contributor.author","Kalthof, Bernd"],["dc.contributor.author","Wiegert, J. Simon"],["dc.contributor.author","König, Gabriele M."],["dc.contributor.author","Kostenis, Evi"],["dc.contributor.author","Patejdl, Robert"],["dc.contributor.author","Sasse, Philipp"],["dc.contributor.author","Bruegmann, Tobias"],["dc.date.accessioned","2022-04-06T07:25:22Z"],["dc.date.available","2022-04-06T07:25:22Z"],["dc.date.issued","2022-04-01"],["dc.description.abstract","Gq proteins are universally important for signal transduction in mammalian cells. The underlying kinetics and transformation from extracellular stimuli into intracellular signaling, however could not be investigated in detail so far. Here we present the human Neuropsin (hOPN5) for specific and repetitive manipulation of Gq signaling in vitro and in vivo with high spatio-temporal resolution. Properties and G protein specificity of hOPN5 are characterized by UV light induced IP3 generation, Ca2+ transients and inhibition of GIRK channel activity in HEK cells. In adult hearts from a transgenic animal model, light increases the spontaneous beating rate. In addition, we demonstrate light induced contractions in the small intestine, which are not detectable after pharmacological Gq protein block. All-optical high-throughput screening for TRPC6 inhibitors is more specific and sensitive than conventional pharmacological screening. Thus, we demonstrate specific Gq signaling of hOPN5 and unveil its potential for optogenetic applications."],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.1038/s41467-022-29265-w"],["dc.identifier.pmid","35365606"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/106429"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/467"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/426"],["dc.language.iso","en"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A14: Gq Protein Aktivierung durch Dehnung der Atrien bei Herzinsuffizienz (HF)"],["dc.relation.issn","2041-1723"],["dc.relation.workinggroup","RG Brügmann (Vegetative Optogenetik)"],["dc.rights","CC BY 4.0"],["dc.title","Selective optogenetic control of Gq signaling using human Neuropsin"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","5562"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","22"],["dc.contributor.affiliation","Rehnelt, Susanne; \t\t \r\n\t\t Institute of Physiology I, Medical Faculty, University of Bonn, 53127 Bonn, Germany, s4surehn@uni-bonn.de"],["dc.contributor.affiliation","Malan, Daniela; \t\t \r\n\t\t Institute of Physiology I, Medical Faculty, University of Bonn, 53127 Bonn, Germany, dmalan@uni-bonn.de"],["dc.contributor.affiliation","Juhasz, Krisztina; \t\t \r\n\t\t Nanion Technologies GmbH, 80636 Munich, Germany, krisztina.juhasz@nanion.de"],["dc.contributor.affiliation","Wolters, Benjamin; \t\t \r\n\t\t Part of the Ncardia Group, Axiogenesis AG, 50829 Cologne, Germany, benjamin.wolters@ncardia.com"],["dc.contributor.affiliation","Doerr, Leo; \t\t \r\n\t\t Nanion Technologies GmbH, 80636 Munich, Germany, leo.doerr@nanion.de"],["dc.contributor.affiliation","Beckler, Matthias; \t\t \r\n\t\t Nanion Technologies GmbH, 80636 Munich, Germany, matthias.beckler@nanion.de"],["dc.contributor.affiliation","Kettenhofen, Ralf; \t\t \r\n\t\t Part of the Ncardia Group, Axiogenesis AG, 50829 Cologne, Germany, ralf.kettenhofen@ncardia.com"],["dc.contributor.affiliation","Bohlen, Heribert; \t\t \r\n\t\t Part of the Ncardia Group, Axiogenesis AG, 50829 Cologne, Germany, heribert.bohlen@ncardia.com"],["dc.contributor.affiliation","Bruegmann, Tobias; \t\t \r\n\t\t Institute of Physiology I, Medical Faculty, University of Bonn, 53127 Bonn, Germany, tobias.bruegmann@med.uni-goettingen.de\t\t \r\n\t\t Research Training Group 1873, University of Bonn, 53127 Bonn, Germany, tobias.bruegmann@med.uni-goettingen.de"],["dc.contributor.affiliation","Sasse, Philipp; \t\t \r\n\t\t Institute of Physiology I, Medical Faculty, University of Bonn, 53127 Bonn, Germany, philipp.sasse@uni-bonn.de"],["dc.contributor.author","Rehnelt, Susanne"],["dc.contributor.author","Malan, Daniela"],["dc.contributor.author","Juhasz, Krisztina"],["dc.contributor.author","Wolters, Benjamin"],["dc.contributor.author","Doerr, Leo"],["dc.contributor.author","Beckler, Matthias"],["dc.contributor.author","Kettenhofen, Ralf"],["dc.contributor.author","Bohlen, Heribert"],["dc.contributor.author","Brügmann, Tobias"],["dc.contributor.author","Sasse, Philipp"],["dc.date.accessioned","2021-07-05T15:00:46Z"],["dc.date.available","2021-07-05T15:00:46Z"],["dc.date.issued","2021"],["dc.date.updated","2022-11-11T13:15:08Z"],["dc.description.abstract","The authors wish to make the following corrections to this paper [...]"],["dc.description.abstract","The authors wish to make the following corrections to this paper [...]"],["dc.identifier.doi","10.3390/ijms22115562"],["dc.identifier.pii","ijms22115562"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/87899"],["dc.language.iso","en"],["dc.notes.intern","DOI Import DOI-Import GROB-441"],["dc.publisher","MDPI"],["dc.relation.eissn","1422-0067"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Addendum: Rehnelt et al. Frequency-Dependent Multi-Well Cardiotoxicity Screening Enabled by Optogenetic Stimulation. Int. J. Mol. Sci. 2017, 18, 2634"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","527"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Pflügers Archiv - European Journal of Physiology"],["dc.bibliographiccitation.lastpage","545"],["dc.bibliographiccitation.volume","472"],["dc.contributor.author","Gundelach, Lili A."],["dc.contributor.author","Hüser, Marc A."],["dc.contributor.author","Beutner, Dirk"],["dc.contributor.author","Ruther, Patrick"],["dc.contributor.author","Brügmann, Tobias"],["dc.date.accessioned","2021-04-14T08:26:51Z"],["dc.date.available","2021-04-14T08:26:51Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1007/s00424-020-02387-0"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/82100"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.eissn","1432-2013"],["dc.relation.issn","0031-6768"],["dc.title","Towards the clinical translation of optogenetic skeletal muscle stimulation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","498"],["dc.bibliographiccitation.journal","Frontiers in Physiology"],["dc.bibliographiccitation.volume","10"],["dc.contributor.author","Funken, Maximilian"],["dc.contributor.author","Malan, Daniela"],["dc.contributor.author","Sasse, Philipp"],["dc.contributor.author","Brügmann, Tobias"],["dc.date.accessioned","2019-07-09T11:51:15Z"],["dc.date.available","2019-07-09T11:51:15Z"],["dc.date.issued","2019"],["dc.description.abstract","Cardiac defibrillation to terminate lethal ventricular arrhythmia (VA) is currently performed by applying high energy electrical shocks. In cardiac tissue, electrical shocks induce simultaneously de- and hyperpolarized areas and only depolarized areas are considered to be responsible for VA termination. Because electrical shocks do not allow proper control over spatial extent and level of membrane potential changes, the effects of hyperpolarization have not been explored in the intact heart. In contrast, optogenetic methods allow cell type-selective induction of de- and hyperpolarization with unprecedented temporal and spatial control. To investigate effects of cardiomyocyte hyperpolarization on VA termination, we generated a mouse line with cardiomyocyte-specific expression of the light-driven proton pump ArchT. Isolated cardiomyocytes showed light-induced outward currents and hyperpolarization. Free-running VA were evoked by electrical stimulation of explanted hearts perfused with low K+ and the KATP channel opener Pinacidil. Optogenetic hyperpolarization was induced by epicardial illumination, which terminated VA with an average efficacy of ∼55%. This value was significantly higher compared to control hearts without illumination or ArchT expression (p = 0.0007). Intracellular recordings with sharp electrodes within the intact heart revealed hyperpolarization and faster action potential upstroke upon illumination, which should fasten conduction. However, conduction speed was lower during illumination suggesting enhanced electrical sink by hyperpolarization underlying VA termination. Thus, selective hyperpolarization in cardiomyocytes is able to terminate VA with a completely new mechanism of increased electrical sink. These novel insights could improve our mechanistic understanding and treatment strategies of VA termination."],["dc.identifier.doi","10.3389/fphys.2019.00498"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/16086"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59908"],["dc.language.iso","en"],["dc.notes.intern","DeepGreen Import"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1664-042X"],["dc.rights","http://creativecommons.org/licenses/by/4.0/"],["dc.subject.ddc","610"],["dc.title","Optogenetic Hyperpolarization of Cardiomyocytes Terminates Ventricular Arrhythmia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","1031062"],["dc.bibliographiccitation.journal","Frontiers in Physiology"],["dc.bibliographiccitation.volume","13"],["dc.contributor.affiliation","Bruegmann, Tobias; \r\n1\r\nInstitute for Cardiovascular Physiology, University Medical Center Goettingen, Goettingen, Germany"],["dc.contributor.affiliation","Smith, Godfrey L.; \r\n4\r\nSchool of Cardiovascular and Metabolic Health, University of Glasgow, Glasgow, United Kingdom"],["dc.contributor.affiliation","Lehnart, Stephan E.; \r\n2\r\nCluster of Excellence “Multiscale Bioimaging: From Molecular Machines to Networks of Excitable Cells“ (MBExC), University of Goettingen, Goettingen, Germany"],["dc.contributor.author","Bruegmann, Tobias"],["dc.contributor.author","Smith, Godfrey L."],["dc.contributor.author","Lehnart, Stephan E."],["dc.date.accessioned","2022-12-01T08:31:34Z"],["dc.date.available","2022-12-01T08:31:34Z"],["dc.date.issued","2022"],["dc.date.updated","2022-11-11T13:12:41Z"],["dc.identifier.doi","10.3389/fphys.2022.1031062"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/118205"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-621"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","1664-042X"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Editorial: Cardiac optogenetics: Using light to observe and excite the heart"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","39"],["dc.bibliographiccitation.journal","Progress in Biophysics and Molecular Biology"],["dc.bibliographiccitation.lastpage","50"],["dc.bibliographiccitation.volume","154"],["dc.contributor.author","Richter, Claudia"],["dc.contributor.author","Brügmann, Tobias"],["dc.date.accessioned","2021-04-14T08:24:33Z"],["dc.date.available","2021-04-14T08:24:33Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1016/j.pbiomolbio.2019.08.013"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81332"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.issn","0079-6107"],["dc.title","No light without the dark: Perspectives and hindrances for translation of cardiac optogenetics"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","176"],["dc.bibliographiccitation.journal","Biomaterials"],["dc.bibliographiccitation.lastpage","190"],["dc.bibliographiccitation.volume","155"],["dc.contributor.author","Ottersbach, Annika"],["dc.contributor.author","Mykhaylyk, Olga"],["dc.contributor.author","Heidsieck, Alexandra"],["dc.contributor.author","Eberbeck, Dietmar"],["dc.contributor.author","Rieck, Sarah"],["dc.contributor.author","Zimmermann, Katrin"],["dc.contributor.author","Breitbach, Martin"],["dc.contributor.author","Engelbrecht, Britta"],["dc.contributor.author","Brügmann, Tobias"],["dc.contributor.author","Hesse, Michael"],["dc.contributor.author","Roell, Wilhelm"],["dc.date.accessioned","2022-03-01T11:44:49Z"],["dc.date.available","2022-03-01T11:44:49Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1016/j.biomaterials.2017.11.012"],["dc.identifier.pii","S014296121730738X"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103132"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","0142-9612"],["dc.rights.uri","https://www.elsevier.com/tdm/userlicense/1.0/"],["dc.title","Improved heart repair upon myocardial infarction: Combination of magnetic nanoparticles and tailored magnets strongly increases engraftment of myocytes"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.contributor.author","Nanadikar, Maithily"],["dc.contributor.author","Leon, Ana Vergel"],["dc.contributor.author","Guo, Jia"],["dc.contributor.author","Belle, Gijsbert van"],["dc.contributor.author","Jatho, Aline"],["dc.contributor.author","Brandner, Astrid"],["dc.contributor.author","Böckmann, Rainer"],["dc.contributor.author","Rhunzu, Shi"],["dc.contributor.author","Brodesser, Susanne"],["dc.contributor.author","Schmidtendorf, Marlen"],["dc.contributor.author","Lee, Jingyun"],["dc.contributor.author","Wu, Hanzhi"],["dc.contributor.author","Furdui, Cristina"],["dc.contributor.author","Burgoyne, Joseph"],["dc.contributor.author","Bogeski, Ivan"],["dc.contributor.author","Riemer, Jan"],["dc.contributor.author","Chowdhury, Arpita"],["dc.contributor.author","Rehling, Peter"],["dc.contributor.author","Bruegmann, Tobias"],["dc.contributor.author","Belousov, Vsevolod"],["dc.contributor.author","Katschinski, Dörthe"],["dc.date.accessioned","2022-05-24T06:56:18Z"],["dc.date.available","2022-05-24T06:56:18Z"],["dc.date.issued","2022"],["dc.identifier.doi","10.21203/rs.3.rs-1594117/v1"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/108252"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/432"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/485"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.workinggroup","RG Brügmann (Vegetative Optogenetik)"],["dc.relation.workinggroup","RG Rehling (Mitochondrial Protein Biogenesis)"],["dc.title","IDH3γ serves as a redox switch that regulates mitochondrial energy metabolism and contractility in the heart under oxidative stress"],["dc.type","preprint"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Physiology"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Cokić, Milan"],["dc.contributor.author","Brügmann, Tobias"],["dc.contributor.author","Sasse, Philipp"],["dc.contributor.author","Malan, Daniela"],["dc.date.accessioned","2022-02-01T10:31:40Z"],["dc.date.available","2022-02-01T10:31:40Z"],["dc.date.issued","2021"],["dc.description.abstract","G-protein signaling pathways are central in the regulation of cardiac function in physiological and pathophysiological conditions. Their functional analysis through optogenetic techniques with selective expression of opsin proteins and activation by specific wavelengths allows high spatial and temporal precision. Here, we present the application of long wavelength-sensitive cone opsin (LWO) in cardiomyocytes for activation of the G i signaling pathway by red light. Murine embryonic stem (ES) cells expressing LWO were generated and differentiated into beating cardiomyocytes in embryoid bodies (EBs). Illumination with red light (625 nm) led to an instantaneous decrease up to complete inhibition (84–99% effectivity) of spontaneous beating, but had no effect on control EBs. By using increasing light intensities with 10 s pulses, we determined a half maximal effective light intensity of 2.4 μW/mm 2 and a maximum effect at 100 μW/mm 2 . Pre-incubation of LWO EBs with pertussis toxin completely inhibited the light effect proving the specificity for G i signaling. Frequency reduction was mainly due to the activation of GIRK channels because the specific channel blocker tertiapin reduced the light effect by ~80%. Compared with pharmacological stimulation of M 2 receptors with carbachol with slow kinetics (>30 s), illumination of LWO had an identical efficacy, but much faster kinetics (<1 s) in the activation and deactivation demonstrating the temporal advantage of optogenetic stimulation. Thus, LWO is an effective optogenetic tool for selective stimulation of the G i signaling cascade in cardiomyocytes with red light, providing high temporal precision."],["dc.description.abstract","G-protein signaling pathways are central in the regulation of cardiac function in physiological and pathophysiological conditions. Their functional analysis through optogenetic techniques with selective expression of opsin proteins and activation by specific wavelengths allows high spatial and temporal precision. Here, we present the application of long wavelength-sensitive cone opsin (LWO) in cardiomyocytes for activation of the G i signaling pathway by red light. Murine embryonic stem (ES) cells expressing LWO were generated and differentiated into beating cardiomyocytes in embryoid bodies (EBs). Illumination with red light (625 nm) led to an instantaneous decrease up to complete inhibition (84–99% effectivity) of spontaneous beating, but had no effect on control EBs. By using increasing light intensities with 10 s pulses, we determined a half maximal effective light intensity of 2.4 μW/mm 2 and a maximum effect at 100 μW/mm 2 . Pre-incubation of LWO EBs with pertussis toxin completely inhibited the light effect proving the specificity for G i signaling. Frequency reduction was mainly due to the activation of GIRK channels because the specific channel blocker tertiapin reduced the light effect by ~80%. Compared with pharmacological stimulation of M 2 receptors with carbachol with slow kinetics (>30 s), illumination of LWO had an identical efficacy, but much faster kinetics (<1 s) in the activation and deactivation demonstrating the temporal advantage of optogenetic stimulation. Thus, LWO is an effective optogenetic tool for selective stimulation of the G i signaling cascade in cardiomyocytes with red light, providing high temporal precision."],["dc.description.sponsorship","Deutsche Forschungsgemeinschaft"],["dc.identifier.doi","10.3389/fphys.2021.768495"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/98921"],["dc.notes.intern","DOI-Import GROB-517"],["dc.relation.eissn","1664-042X"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Optogenetic Stimulation of Gi Signaling Enables Instantaneous Modulation of Cardiomyocyte Pacemaking"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2634"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","International Journal of Molecular Sciences"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Rehnelt, Susanne"],["dc.contributor.author","Malan, Daniela"],["dc.contributor.author","Juhasz, Krisztina"],["dc.contributor.author","Wolters, Benjamin"],["dc.contributor.author","Doerr, Leo"],["dc.contributor.author","Beckler, Matthias"],["dc.contributor.author","Kettenhofen, Ralf"],["dc.contributor.author","Bohlen, Heribert"],["dc.contributor.author","Brügmann, Tobias"],["dc.contributor.author","Sasse, Philipp"],["dc.date.accessioned","2022-03-01T11:44:26Z"],["dc.date.available","2022-03-01T11:44:26Z"],["dc.date.issued","2017"],["dc.description.abstract","Side effects on cardiac ion channels causing lethal arrhythmias are one major reason for drug withdrawals from the market. Field potential (FP) recording from cardiomyocytes, is a well-suited tool to assess such cardiotoxic effects of drug candidates in preclinical drug development, but it is currently limited to the spontaneous beating of the cardiomyocytes and manual analysis. Herein, we present a novel optogenetic cardiotoxicity screening system suited for the parallel automated frequency-dependent analysis of drug effects on FP recorded from human pluripotent stem cell-derived cardiomyocytes. For the expression of the light-sensitive cation channel Channelrhodopsin-2, we optimised protocols using virus transduction or transient mRNA transfection. Optical stimulation was performed with a new light-emitting diode lid for a 96-well FP recording system. This enabled reliable pacing at physiologically relevant heart rates and robust recording of FP. Thereby we detected rate-dependent effects of drugs on Na+, Ca2+ and K+ channel function indicated by FP prolongation, FP shortening and the slowing of the FP downstroke component, as well as generation of afterdepolarisations. Taken together, we present a scalable approach for preclinical frequency-dependent screening of drug effects on cardiac electrophysiology. Importantly, we show that the recording and analysis can be fully automated and the technology is readily available using commercial products."],["dc.description.abstract","Side effects on cardiac ion channels causing lethal arrhythmias are one major reason for drug withdrawals from the market. Field potential (FP) recording from cardiomyocytes, is a well-suited tool to assess such cardiotoxic effects of drug candidates in preclinical drug development, but it is currently limited to the spontaneous beating of the cardiomyocytes and manual analysis. Herein, we present a novel optogenetic cardiotoxicity screening system suited for the parallel automated frequency-dependent analysis of drug effects on FP recorded from human pluripotent stem cell-derived cardiomyocytes. For the expression of the light-sensitive cation channel Channelrhodopsin-2, we optimised protocols using virus transduction or transient mRNA transfection. Optical stimulation was performed with a new light-emitting diode lid for a 96-well FP recording system. This enabled reliable pacing at physiologically relevant heart rates and robust recording of FP. Thereby we detected rate-dependent effects of drugs on Na+, Ca2+ and K+ channel function indicated by FP prolongation, FP shortening and the slowing of the FP downstroke component, as well as generation of afterdepolarisations. Taken together, we present a scalable approach for preclinical frequency-dependent screening of drug effects on cardiac electrophysiology. Importantly, we show that the recording and analysis can be fully automated and the technology is readily available using commercial products."],["dc.identifier.doi","10.3390/ijms18122634"],["dc.identifier.pii","ijms18122634"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103023"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","1422-0067"],["dc.title","Frequency-Dependent Multi-Well Cardiotoxicity Screening Enabled by Optogenetic Stimulation"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]