Now showing 1 - 3 of 3
  • 2020Journal Article
    [["dc.bibliographiccitation.firstpage","1790"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.lastpage","1801"],["dc.bibliographiccitation.volume","117"],["dc.contributor.author","Fakuade, Funsho E"],["dc.contributor.author","Steckmeister, Vanessa"],["dc.contributor.author","Seibertz, Fitzwilliam"],["dc.contributor.author","Gronwald, Judith"],["dc.contributor.author","Kestel, Stefanie"],["dc.contributor.author","Menzel, Julia"],["dc.contributor.author","Pronto, Julius Ryan D"],["dc.contributor.author","Taha, Karim"],["dc.contributor.author","Haghighi, Fereshteh"],["dc.contributor.author","Voigt, Niels"],["dc.date.accessioned","2021-08-12T07:45:13Z"],["dc.date.available","2021-08-12T07:45:13Z"],["dc.date.issued","2020"],["dc.description.abstract","Abstract Aims  Atrial fibrillation (AF) is a commonly occurring arrhythmia after cardiac surgery (postoperative AF, poAF) and is associated with poorer outcomes. Considering that reduced atrial contractile function is a predictor of poAF and that Ca2+ plays an important role in both excitation–contraction coupling and atrial arrhythmogenesis, this study aims to test whether alterations of intracellular Ca2+ handling contribute to impaired atrial contractility and to the arrhythmogenic substrate predisposing patients to poAF. Methods and results  Right atrial appendages were obtained from patients in sinus rhythm undergoing open-heart surgery. Cardiomyocytes were investigated by simultaneous measurement of [Ca2+]i and action potentials (APs, patch-clamp). Patients were followed-up for 6 days to identify those with and without poAF. Speckle-tracking analysis of preoperative echocardiography revealed reduced left atrial contraction strain in poAF patients. At the time of surgery, cellular Ca2+ transients (CaTs) and the sarcoplasmic reticulum (SR) Ca2+ content were smaller in the poAF group. CaT decay was slower in poAF, but the decay of caffeine-induced Ca2+ transients was unaltered, suggesting preserved sodium-calcium exchanger function. In agreement, western blots revealed reduced SERCA2a expression in poAF patients but unaltered phospholamban expression/phosphorylation. Computational modelling indicated that reduced SERCA activity promotes occurrence of CaT and AP alternans. Indeed, alternans of CaT and AP occurred more often and at lower stimulation frequencies in atrial myocytes from poAF patients. Resting membrane potential and AP duration were comparable between both groups at various pacing frequencies (0.25–8 Hz). Conclusions  Biochemical, functional, and modelling data implicate reduced SERCA-mediated Ca2+ reuptake into the SR as a major contributor to impaired preoperative atrial contractile function and to the pre-existing arrhythmogenic substrate in patients developing poAF."],["dc.description.abstract","Abstract Aims  Atrial fibrillation (AF) is a commonly occurring arrhythmia after cardiac surgery (postoperative AF, poAF) and is associated with poorer outcomes. Considering that reduced atrial contractile function is a predictor of poAF and that Ca2+ plays an important role in both excitation–contraction coupling and atrial arrhythmogenesis, this study aims to test whether alterations of intracellular Ca2+ handling contribute to impaired atrial contractility and to the arrhythmogenic substrate predisposing patients to poAF. Methods and results  Right atrial appendages were obtained from patients in sinus rhythm undergoing open-heart surgery. Cardiomyocytes were investigated by simultaneous measurement of [Ca2+]i and action potentials (APs, patch-clamp). Patients were followed-up for 6 days to identify those with and without poAF. Speckle-tracking analysis of preoperative echocardiography revealed reduced left atrial contraction strain in poAF patients. At the time of surgery, cellular Ca2+ transients (CaTs) and the sarcoplasmic reticulum (SR) Ca2+ content were smaller in the poAF group. CaT decay was slower in poAF, but the decay of caffeine-induced Ca2+ transients was unaltered, suggesting preserved sodium-calcium exchanger function. In agreement, western blots revealed reduced SERCA2a expression in poAF patients but unaltered phospholamban expression/phosphorylation. Computational modelling indicated that reduced SERCA activity promotes occurrence of CaT and AP alternans. Indeed, alternans of CaT and AP occurred more often and at lower stimulation frequencies in atrial myocytes from poAF patients. Resting membrane potential and AP duration were comparable between both groups at various pacing frequencies (0.25–8 Hz). Conclusions  Biochemical, functional, and modelling data implicate reduced SERCA-mediated Ca2+ reuptake into the SR as a major contributor to impaired preoperative atrial contractile function and to the pre-existing arrhythmogenic substrate in patients developing poAF."],["dc.identifier.doi","10.1093/cvr/cvaa162"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/88398"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-448"],["dc.relation.eissn","1755-3245"],["dc.relation.issn","0008-6363"],["dc.title","Altered atrial cytosolic calcium handling contributes to the development of postoperative atrial fibrillation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]
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  • 2020Journal Article Research Paper
    [["dc.bibliographiccitation.issue","166"],["dc.bibliographiccitation.journal","Journal of Visualized Experiments"],["dc.contributor.author","Seibertz, Fitzwilliam"],["dc.contributor.author","Reynolds, Martyn"],["dc.contributor.author","Voigt, Niels"],["dc.date.accessioned","2021-06-01T09:42:44Z"],["dc.date.available","2021-06-01T09:42:44Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.3791/61890"],["dc.identifier.pmid","33427238"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/85333"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/128"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-425"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation.eissn","1940-087X"],["dc.relation.workinggroup","RG Voigt (Molecular Pharmacology)"],["dc.title","Single-Cell Optical Action Potential Measurement in Human Induced Pluripotent Stem Cell-Derived Cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]
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  • 2022Journal Article
    [["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Communications Biology"],["dc.bibliographiccitation.volume","5"],["dc.contributor.author","Seibertz, Fitzwilliam"],["dc.contributor.author","Rapedius, Markus"],["dc.contributor.author","Fakuade, Funsho E."],["dc.contributor.author","Tomsits, Philipp"],["dc.contributor.author","Liutkute, Aiste"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Becker, Nadine"],["dc.contributor.author","Majumder, Rupamanjari"],["dc.contributor.author","Clauß, Sebastian"],["dc.contributor.author","Fertig, Niels"],["dc.contributor.author","Voigt, Niels"],["dc.date.accessioned","2022-10-04T10:21:07Z"],["dc.date.available","2022-10-04T10:21:07Z"],["dc.date.issued","2022"],["dc.description.abstract","Abstract\n Crucial conventional patch-clamp approaches to investigate cellular electrophysiology suffer from low-throughput and require considerable experimenter expertise. Automated patch-clamp (APC) approaches are more experimenter independent and offer high-throughput, but by design are predominantly limited to assays containing small, homogenous cells. In order to enable high-throughput APC assays on larger cells such as native cardiomyocytes isolated from mammalian hearts, we employed a fixed-well APC plate format. A broad range of detailed electrophysiological parameters including action potential, L-type calcium current and basal inward rectifier current were reliably acquired from isolated swine atrial and ventricular cardiomyocytes using APC. Effective pharmacological modulation also indicated that this technique is applicable for drug screening using native cardiomyocyte material. Furthermore, sequential acquisition of multiple parameters from a single cell was successful in a high throughput format, substantially increasing data richness and quantity per experimental run. When appropriately expanded, these protocols will provide a foundation for effective mechanistic and phenotyping studies of human cardiac electrophysiology. Utilizing scarce biopsy samples, regular high throughput characterization of primary cardiomyocytes using APC will facilitate drug development initiatives and personalized treatment strategies for a multitude of cardiac diseases."],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft https://doi.org/10.13039/501100001659"],["dc.description.sponsorship"," Deutsches Zentrum für Herz-Kreislaufforschung https://doi.org/10.13039/100010447"],["dc.identifier.doi","10.1038/s42003-022-03871-2"],["dc.identifier.pii","3871"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/114333"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-600"],["dc.relation.eissn","2399-3642"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","A modern automated patch-clamp approach for high throughput electrophysiology recordings in native cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]
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