Brügmann, Tobias

[["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"]]

[["dc.bibliographiccitation.artnumber","1643"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Lapp, Hendrik"],["dc.contributor.author","Brügmann, Tobias"],["dc.contributor.author","Malan, Daniela"],["dc.contributor.author","Friedrichs, Stephanie"],["dc.contributor.author","Kilgus, Carsten"],["dc.contributor.author","Heidsieck, Alexandra"],["dc.contributor.author","Sasse, Philipp"],["dc.date.accessioned","2022-03-01T11:46:04Z"],["dc.date.available","2022-03-01T11:46:04Z"],["dc.date.issued","2021"],["dc.description.abstract","An amendment to this paper has been published and can be accessed via a link at the top of the paper."],["dc.identifier.doi","10.1038/s41598-020-80763-7"],["dc.identifier.pii","80763"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103548"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.eissn","2045-2322"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Author Correction: Frequency-dependent drug screening using optogenetic stimulation of human iPSC-derived cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.subtype","erratum_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","527a"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.volume","98"],["dc.contributor.author","Brügmann, Tobias"],["dc.contributor.author","Fleischmann, Bernd K."],["dc.contributor.author","Sasse, Philipp"],["dc.date.accessioned","2022-03-01T11:44:53Z"],["dc.date.available","2022-03-01T11:44:53Z"],["dc.date.issued","2010"],["dc.identifier.doi","10.1016/j.bpj.2009.12.2860"],["dc.identifier.pii","S0006349509046657"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103150"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","0006-3495"],["dc.title","Light-Induced Depolarization to Stimulate Cardiomyocytes with High Spatio-Temporal Resolution and to Modulate their Differentiation in Vitro"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","678a"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.volume","104"],["dc.contributor.author","Beiert, Thomas"],["dc.contributor.author","Brügmann, Tobias"],["dc.contributor.author","Fleischmann, Bernd K."],["dc.contributor.author","Sasse, Philipp"],["dc.date.accessioned","2022-03-01T11:44:57Z"],["dc.date.available","2022-03-01T11:44:57Z"],["dc.date.issued","2013"],["dc.identifier.doi","10.1016/j.bpj.2012.11.3745"],["dc.identifier.pii","S0006349512049910"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103170"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","0006-3495"],["dc.title","Optogenetic Gq Signaling in Cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","678a"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.volume","104"],["dc.contributor.author","Brügmann, Tobias"],["dc.contributor.author","Vosen, Sarah"],["dc.contributor.author","Wenzel, Daniela"],["dc.contributor.author","Fleischmann, Bernd K."],["dc.contributor.author","Sasse, Philipp"],["dc.date.accessioned","2022-03-01T11:44:57Z"],["dc.date.available","2022-03-01T11:44:57Z"],["dc.date.issued","2013"],["dc.identifier.doi","10.1016/j.bpj.2012.11.3742"],["dc.identifier.pii","S0006349512049880"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103169"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","0006-3495"],["dc.title","Optogenetic Control of Vascular Tone with High Temporal Resolution"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","17100"],["dc.bibliographiccitation.issue","50"],["dc.bibliographiccitation.journal","Journal of Biological Chemistry"],["dc.bibliographiccitation.lastpage","17113"],["dc.bibliographiccitation.volume","295"],["dc.contributor.author","Wang-Eckhardt, Lihua"],["dc.contributor.author","Bastian, Asisa"],["dc.contributor.author","Brügmann, Tobias"],["dc.contributor.author","Sasse, Philipp"],["dc.contributor.author","Eckhardt, Matthias"],["dc.date.accessioned","2021-04-14T08:25:52Z"],["dc.date.available","2021-04-14T08:25:52Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.1074/jbc.RA120.014188"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/81756"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-399"],["dc.relation.issn","0021-9258"],["dc.title","Carnosine synthase deficiency is compatible with normal skeletal muscle and olfactory function but causes reduced olfactory sensitivity in aging mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","201"],["dc.bibliographiccitation.journal","Journal of Pharmacological and Toxicological Methods"],["dc.bibliographiccitation.volume","75"],["dc.contributor.author","Zamora, Victor"],["dc.contributor.author","Hortigon-Vinagre, Maria Pura"],["dc.contributor.author","Brügmann, Tobias"],["dc.contributor.author","Costa, Ana"],["dc.contributor.author","Craig, Margaret Anne"],["dc.contributor.author","Burton, Francis"],["dc.contributor.author","Sasse, Philipp"],["dc.contributor.author","Smith, Godfrey"],["dc.date.accessioned","2022-03-01T11:45:24Z"],["dc.date.available","2022-03-01T11:45:24Z"],["dc.date.issued","2015"],["dc.identifier.doi","10.1016/j.vascn.2015.08.145"],["dc.identifier.pii","S1056871915002397"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103316"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","1056-8719"],["dc.title","Rapid intensity modulation of a single light source allows excitation of a voltage sensitive dye and intermittent activation of channel rhodopsin in hiPSC derived cardiomyocytes (hiPSC-CMs)"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","jcsm.13026"],["dc.bibliographiccitation.journal","Journal of Cachexia, Sarcopenia and Muscle"],["dc.contributor.author","Kimoloi, Sammy"],["dc.contributor.author","Sen, Ayesha"],["dc.contributor.author","Guenther, Stefan"],["dc.contributor.author","Braun, Thomas"],["dc.contributor.author","Brügmann, Tobias"],["dc.contributor.author","Sasse, Philipp"],["dc.contributor.author","Wiesner, Rudolf J."],["dc.contributor.author","Pla‐Martín, David"],["dc.contributor.author","Baris, Olivier R."],["dc.date.accessioned","2022-07-01T07:34:58Z"],["dc.date.available","2022-07-01T07:34:58Z"],["dc.date.issued","2022"],["dc.identifier.doi","10.1002/jcsm.13026"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112051"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-581"],["dc.relation.eissn","2190-6009"],["dc.relation.issn","2190-5991"],["dc.title","Combined fibre atrophy and decreased muscle regeneration capacity driven by mitochondrial DNA alterations underlie the development of sarcopenia"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","489a"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.volume","114"],["dc.contributor.author","Rizzetto, Riccardo"],["dc.contributor.author","Agus, Viviana"],["dc.contributor.author","Pizzi, Sara"],["dc.contributor.author","Rolland, Jean-Francois"],["dc.contributor.author","Scarabottolo, Lia"],["dc.contributor.author","Renhelt, Susanne"],["dc.contributor.author","Malan, Daniela"],["dc.contributor.author","Brügmann, Tobias"],["dc.contributor.author","Sasse, Philipp"],["dc.contributor.author","Juhasz, Krisztina"],["dc.contributor.author","Fertig, Niels"],["dc.date.accessioned","2022-03-01T11:44:58Z"],["dc.date.available","2022-03-01T11:44:58Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1016/j.bpj.2017.11.2681"],["dc.identifier.pii","S0006349517339139"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103179"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","0006-3495"],["dc.title","Optogenetic Technologies Enable High Throughput Ion Channel Drug Discovery and Toxicity Screening"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]