Cyganek, Lukas

[["dc.bibliographiccitation.firstpage","1928"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Europace"],["dc.bibliographiccitation.lastpage","1929"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","El-Battrawy, Ibrahim"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Zhou, Xiaobo"],["dc.contributor.author","Akin, Ibrahim"],["dc.date.accessioned","2020-12-10T18:19:09Z"],["dc.date.available","2020-12-10T18:19:09Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1093/europace/euz274"],["dc.identifier.eissn","1532-2092"],["dc.identifier.issn","1099-5129"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/75144"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","‘Mature’ resting membrane potentials in hiPSC-CMs: fact or artefact?—Authors’ reply"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1"],["dc.bibliographiccitation.journal","Stem Cells International"],["dc.bibliographiccitation.lastpage","14"],["dc.bibliographiccitation.volume","2018"],["dc.contributor.author","Zhao, Zhihan"],["dc.contributor.author","Lan, Huan"],["dc.contributor.author","El-Battrawy, Ibrahim"],["dc.contributor.author","Li, Xin"],["dc.contributor.author","Buljubasic, Fanis"],["dc.contributor.author","Sattler, Katherine"],["dc.contributor.author","Yücel, Gökhan"],["dc.contributor.author","Lang, Siegfried"],["dc.contributor.author","Tiburcy, Malte"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Utikal, Jochen"],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Borggrefe, Martin"],["dc.contributor.author","Zhou, Xiao-Bo"],["dc.contributor.author","Akin, Ibrahim"],["dc.date.accessioned","2020-12-10T18:37:41Z"],["dc.date.available","2020-12-10T18:37:41Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1155/2018/6067096"],["dc.identifier.pmid","29535773"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77065"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/325"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Ion Channel Expression and Characterization 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"]]

[["dc.bibliographiccitation.firstpage","112"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of Cardiovascular Development and Disease"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Xu, Qiang"],["dc.contributor.author","Huang, Xuemei"],["dc.contributor.author","Meng, Zenghui"],["dc.contributor.author","Li, Yingrui"],["dc.contributor.author","Zhong, Rujia"],["dc.contributor.author","Li, Xin"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","El-Battrawy, Ibrahim"],["dc.contributor.author","Akin, Ibrahim"],["dc.contributor.author","Zhou, Xiaobo"],["dc.contributor.author","Lan, Huan"],["dc.date.accessioned","2022-05-02T08:09:37Z"],["dc.date.available","2022-05-02T08:09:37Z"],["dc.date.issued","2022"],["dc.description.abstract","(1) Background: Short QT syndrome (SQTS) may result in sudden cardiac death. So far, no drugs, except quinidine, have been demonstrated to be effective in some patients with SQTS type 1 (SQTS1). This study was designed to examine the potential effectiveness of vernakalant for treating SQTS1 patients, using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a patient with SQTS1. (2) Methods: Patch clamp and calcium imaging techniques were used to examine the drug effects. (3) Results: Vernakalant prolonged the action potential duration (APD) in hiPSC-CMs from a SQTS1-patient (SQTS1-hiPSC-CMs). In spontaneously beating SQTS1-hiPSC-CMs, vernakalant reduced the arrhythmia-like events induced by carbachol plus epinephrine. Vernakalant failed to suppress the hERG channel currents but reduced the outward small-conductance calcium-activated potassium channel current. In addition, it enhanced Na/Ca exchanger currents and late sodium currents, in agreement with its APD-prolonging effect. (4) Conclusions: The results demonstrated that vernakalant can prolong APD and reduce arrhythmia-like events in SQTS1-hiPSC-CMs and may be a candidate drug for treating arrhythmias in SQTS1-patients."],["dc.description.abstract","(1) Background: Short QT syndrome (SQTS) may result in sudden cardiac death. So far, no drugs, except quinidine, have been demonstrated to be effective in some patients with SQTS type 1 (SQTS1). This study was designed to examine the potential effectiveness of vernakalant for treating SQTS1 patients, using human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a patient with SQTS1. (2) Methods: Patch clamp and calcium imaging techniques were used to examine the drug effects. (3) Results: Vernakalant prolonged the action potential duration (APD) in hiPSC-CMs from a SQTS1-patient (SQTS1-hiPSC-CMs). In spontaneously beating SQTS1-hiPSC-CMs, vernakalant reduced the arrhythmia-like events induced by carbachol plus epinephrine. Vernakalant failed to suppress the hERG channel currents but reduced the outward small-conductance calcium-activated potassium channel current. In addition, it enhanced Na/Ca exchanger currents and late sodium currents, in agreement with its APD-prolonging effect. (4) Conclusions: The results demonstrated that vernakalant can prolong APD and reduce arrhythmia-like events in SQTS1-hiPSC-CMs and may be a candidate drug for treating arrhythmias in SQTS1-patients."],["dc.identifier.doi","10.3390/jcdd9040112"],["dc.identifier.pii","jcdd9040112"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/107421"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-561"],["dc.relation.eissn","2308-3425"],["dc.title","Antiarrhythmic Effects of Vernakalant in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes from a Patient with Short QT Syndrome Type 1"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1140"],["dc.bibliographiccitation.issue","10"],["dc.bibliographiccitation.journal","Clinical Research in Cardiology"],["dc.bibliographiccitation.lastpage","1146"],["dc.bibliographiccitation.volume","108"],["dc.contributor.author","El-Battrawy, Ibrahim"],["dc.contributor.author","Besler, Johanna"],["dc.contributor.author","Ansari, Uzair"],["dc.contributor.author","Liebe, Volker"],["dc.contributor.author","Schimpf, Rainer"],["dc.contributor.author","Tülümen, Erol"],["dc.contributor.author","Rudic, Boris"],["dc.contributor.author","Lang, Siegfried"],["dc.contributor.author","Odening, Katja"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Wolpert, Christian"],["dc.contributor.author","Zhou, Xiaobo"],["dc.contributor.author","Borggrefe, Martin"],["dc.contributor.author","Akin, Ibrahim"],["dc.date.accessioned","2020-12-10T14:10:22Z"],["dc.date.available","2020-12-10T14:10:22Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1007/s00392-019-01449-3"],["dc.identifier.eissn","1861-0692"],["dc.identifier.issn","1861-0684"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/70740"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Long-term follow-up of implantable cardioverter-defibrillators in Short QT syndrome"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1410"],["dc.bibliographiccitation.issue","9"],["dc.bibliographiccitation.journal","Europace"],["dc.bibliographiccitation.lastpage","1421"],["dc.bibliographiccitation.volume","21"],["dc.contributor.author","El-Battrawy, Ibrahim"],["dc.contributor.author","Albers, Sebastian"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Zhao, Zhihan"],["dc.contributor.author","Lan, Huan"],["dc.contributor.author","Li, Xin"],["dc.contributor.author","Xu, Qiang"],["dc.contributor.author","Kleinsorge, Mandy"],["dc.contributor.author","Huang, Mengying"],["dc.contributor.author","Liao, Zhenxing"],["dc.contributor.author","Zhong, Rujia"],["dc.contributor.author","Rudic, Boris"],["dc.contributor.author","Müller, Jonas"],["dc.contributor.author","Dinkel, Hendrik"],["dc.contributor.author","Lang, Siegfried"],["dc.contributor.author","Diecke, Sebastian"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Utikal, Jochen"],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Borggrefe, Martin"],["dc.contributor.author","Zhou, Xiaobo"],["dc.contributor.author","Akin, Ibrahim"],["dc.date.accessioned","2020-12-10T18:19:09Z"],["dc.date.available","2020-12-10T18:19:09Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1093/europace/euz122"],["dc.identifier.pmid","31106349"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/75142"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/328"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","A cellular model of Brugada syndrome with SCN10A variants using human-induced pluripotent stem cell-derived cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","2935"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","Yücel, Gökhan"],["dc.contributor.author","Zhao, Zhihan"],["dc.contributor.author","El-Battrawy, Ibrahim"],["dc.contributor.author","Lan, Huan"],["dc.contributor.author","Lang, Siegfried"],["dc.contributor.author","Li, Xin"],["dc.contributor.author","Buljubasic, Fanis"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Utikal, Jochen"],["dc.contributor.author","Ravens, Ursula"],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Borggrefe, Martin"],["dc.contributor.author","Zhou, Xiao-Bo"],["dc.contributor.author","Akin, Ibrahim"],["dc.date.accessioned","2018-04-23T11:49:22Z"],["dc.date.available","2018-04-23T11:49:22Z"],["dc.date.issued","2017"],["dc.description.abstract","Severe infections like sepsis lead frequently to cardiomyopathy. The mechanisms are unclear and an optimal therapy for septic cardiomyopathy still lacks. The aim of this study is to establish an endotoxin-induced inflammatory model using human induced pluripotent stem cell (hiPSC) derived cardiomyocytes (hiPSC-CMs) for mechanistic and therapeutic studies. hiPSC-CMs were treated by lipopolysaccharide (LPS) in different concentrations for different times. ELISA, FACS, qPCR, and patch-clamp techniques were used for the study. TLR4 (Toll-like receptor 4) and its associated proteins, CD14, LBP (lipopolysaccharide binding protein), TIRAP (toll-interleukin 1 receptor domain containing adaptor protein), Ly96 (lymphocyte antigen 96) and nuclear factor kappa B as well as some pro-and anti-inflammatory factors are expressed in hiPSC-CMs. LPS-treatment for 6 hours increased the expression levels of pro-inflammatory and chemotactic cytokines (TNF-a, IL-1ß, IL-6, CCL2, CCL5, IL-8), whereas 48 hour-treatment elevated the expression of anti-inflammatory factors (IL-10 and IL-6). LPS led to cell injury resulting from exaggerated cell apoptosis and necrosis. Finally, LPS inhibited small conductance Ca2+-activated K+ channel currents, enhanced Na+/Ca2+-exchanger currents, prolonged action potential duration, suggesting cellular electrical dysfunctions. Our data demonstrate that hiPSC-CMs possess the functional reaction system involved in endotoxin-induced inflammation and can model some bacterium-induced inflammatory responses in cardiac myocytes."],["dc.identifier.doi","10.1038/s41598-017-03147-4"],["dc.identifier.gro","3142526"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/14783"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13682"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.relation.issn","2045-2322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Lipopolysaccharides induced inflammatory responses and electrophysiological dysfunctions in human-induced pluripotent stem cell derived cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","14689"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Sattler, Katherine"],["dc.contributor.author","El-Battrawy, Ibrahim"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Lang, Siegfried"],["dc.contributor.author","Lan, Huan"],["dc.contributor.author","Li, Xin"],["dc.contributor.author","Zhao, Zhihan"],["dc.contributor.author","Utikal, Jochen"],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Borggrefe, Martin"],["dc.contributor.author","Akin, Ibrahim"],["dc.date.accessioned","2021-09-01T06:42:20Z"],["dc.date.available","2021-09-01T06:42:20Z"],["dc.date.issued","2021"],["dc.description.abstract","Abstract The non-selective cation channel transient receptor potential vanilloid 1 (TRPV1) is expressed throughout the cardiovascular system. Recent evidence shows a role for TRPV1 in inflammatory processes. The role of TRPV1 for myocardial inflammation has not been established yet. Human induced pluripotent stem cell (iPSC)-derived cardiomyocytes (hiPSC-CM) from 4 healthy donors were incubated with lipopolysaccharides (LPS, 6 h), TRPV1 agonist capsaicin (CAP, 20 min) or the antagonist capsazepine (CPZ, 20 min). TRPV1 expression was studied by PCR and western blotting. TRPV1 internalization was analyzed by immunofluorescence. Interleukin-6 (IL-6) secretion and phosphorylation of JNK, p38 and ERK were determined by ELISA. TRPV1-associated ion channel current was measured by patch clamp. TRPV1-mRNA and -protein were expressed in hiPSC-CM. TRPV1 was localized in the plasma membrane. LPS significantly increased secretion of IL-6 by 2.3-fold, which was prevented by pre-incubation with CPZ. LPS induced TRPV1 internalization. Phosphorylation levels of ERK, p38 or JNK were not altered by TRPV1 stimulation or inhibition. LPS and IL-6 significantly lowered TRPV1-mediated ion channel current. TRPV1 mediates the LPS-induced inflammation in cardiomyocytes, associated with changes of cellular electrophysiology. LPS-induced inflammation results in TRPV1 internalization. Further studies have to examine the underlying pathways and the clinical relevance of these findings."],["dc.identifier.doi","10.1038/s41598-021-93958-3"],["dc.identifier.pii","93958"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/89034"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/399"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-455"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | S01: In vivo und in vitro Krankheitsmodelle"],["dc.relation.eissn","2045-2322"],["dc.relation.workinggroup","RG Cyganek (Stem Cell Unit)"],["dc.rights","CC BY 4.0"],["dc.title","TRPV1 activation and internalization is part of the LPS-induced inflammation in human iPSC-derived cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Cardiovascular Medicine"],["dc.bibliographiccitation.volume","8"],["dc.contributor.author","Huang, Mengying"],["dc.contributor.author","Yang, Zhen"],["dc.contributor.author","Li, Yingrui"],["dc.contributor.author","Lan, Huan"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Yuecel, Goekhan"],["dc.contributor.author","Lang, Siegfried"],["dc.contributor.author","Bieback, Karen"],["dc.contributor.author","El-Battrawy, Ibrahim"],["dc.contributor.author","Zhou, Xiaobo"],["dc.contributor.author","Akin, Ibrahim"],["dc.date.accessioned","2022-04-01T10:01:10Z"],["dc.date.available","2022-04-01T10:01:10Z"],["dc.date.issued","2022"],["dc.description.abstract","Background Previous studies suggested involvement of non-ß-adrenoceptors in the pathogenesis of Takotsubo cardiomyopathy (TTC). This study was designed to explore possible roles and underlying mechanisms of dopamine D1/D5 receptor coupled signaling in arrhythmogenesis of TTC. Methods Human-induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) were challenged by toxic concentration of epinephrine (Epi, 0.5 mM for 1 h) for mimicking the catecholamine excess in setting of TTC. Specific receptor blockers and activators were used to unveil roles of D1/D5 receptors. Patch clamp, qPCR, and FACS analyses were performed in the study. Results High concentration Epi and two dopamine D1/D5 receptor agonists [(±)-SKF 38393 and fenoldopam] reduced the depolarization velocity and prolonged the duration of action potentials (APs) and caused arrhythmic events in iPSC-CMs, suggesting involvement of dopamine D1/D5 receptor signaling in arrhythmogenesis associated with QT interval prolongation in the setting of TTC. (±)-SKF 38393 and fenoldopam enhanced the reactive oxygen species (ROS)-production. H 2 O 2 (100 μM) recapitulated the effects of (±)-SKF 38393 and fenoldopam on APs and a ROS-blocker N -acetylcysteine (NAC, 1 mM) abolished the effects, suggesting that the ROS-signaling is involved in the dopamine D1/D5 receptor actions. A NADPH oxidases blocker and a PKA- or PKC-blocker suppressed the effects of the dopamine receptor agonist, implying that PKA, NADPH oxidases and PKC participated in dopamine D1/D5 receptor signaling. The abnormal APs resulted from dopamine D1/D5 receptor activation-induced dysfunctions of ion channels including the Na + and L-type Ca 2+ and I Kr channels. Conclusions Dopamine D1/D5 receptor signaling plays important roles for arrhythmogenesis of TTC. Dopamine D1/D5 receptor signaling in cardiomyocytes might be a potential target for treating arrhythmias in patients with TTC."],["dc.identifier.doi","10.3389/fcvm.2021.777463"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/105614"],["dc.notes.intern","DOI-Import GROB-530"],["dc.relation.eissn","2297-055X"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0/"],["dc.title","Dopamine D1/D5 Receptor Signaling Is Involved in Arrhythmogenesis in the Setting of Takotsubo Cardiomyopathy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","486"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Journal of Clinical Medicine"],["dc.bibliographiccitation.volume","9"],["dc.contributor.author","Buljubasic, Fanis"],["dc.contributor.author","El-Battrawy, Ibrahim"],["dc.contributor.author","Lan, Huan"],["dc.contributor.author","Lomada, Santosh K."],["dc.contributor.author","Chatterjee, Anupriya"],["dc.contributor.author","Zhao, Zhihan"],["dc.contributor.author","Li, Xin"],["dc.contributor.author","Zhong, Rujia"],["dc.contributor.author","Xu, Qiang"],["dc.contributor.author","Huang, Mengying"],["dc.contributor.author","Liao, Zhenxing"],["dc.contributor.author","Lang, Siegfried"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Zhou, Xiaobo"],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Borggrefe, Martin"],["dc.contributor.author","Akin, Ibrahim"],["dc.date.accessioned","2020-12-10T18:47:12Z"],["dc.date.available","2020-12-10T18:47:12Z"],["dc.date.issued","2020"],["dc.identifier.doi","10.3390/jcm9020486"],["dc.identifier.eissn","2077-0383"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78680"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Nucleoside Diphosphate Kinase B Contributes to Arrhythmogenesis in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes from a Patient with Arrhythmogenic Right Ventricular Cardiomyopathy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","Frontiers in Cell and Developmental Biology"],["dc.bibliographiccitation.volume","7"],["dc.contributor.author","El-Battrawy, Ibrahim"],["dc.contributor.author","Müller, Jonas"],["dc.contributor.author","Zhao, Zhihan"],["dc.contributor.author","Cyganek, Lukas"],["dc.contributor.author","Zhong, Rujia"],["dc.contributor.author","Zhang, Feng"],["dc.contributor.author","Kleinsorge, Mandy"],["dc.contributor.author","Lan, Huan"],["dc.contributor.author","Li, Xin"],["dc.contributor.author","Xu, Qiang"],["dc.contributor.author","Huang, Mengying"],["dc.contributor.author","Liao, Zhenxing"],["dc.contributor.author","Moscu-Gregor, Alexander"],["dc.contributor.author","Albers, Sebastian"],["dc.contributor.author","Dinkel, Hendrik"],["dc.contributor.author","Lang, Siegfried"],["dc.contributor.author","Diecke, Sebastian"],["dc.contributor.author","Zimmermann, Wolfram-Hubertus"],["dc.contributor.author","Utikal, Jochen"],["dc.contributor.author","Wieland, Thomas"],["dc.contributor.author","Borggrefe, Martin"],["dc.contributor.author","Zhou, Xiaobo"],["dc.contributor.author","Akin, Ibrahim"],["dc.date.accessioned","2020-12-10T18:44:21Z"],["dc.date.available","2020-12-10T18:44:21Z"],["dc.date.issued","2019"],["dc.description.abstract","Background Among rare channelopathies BrS patients are at high risk of sudden cardiac death (SCD). SCN5A mutations are found in a quarter of patients. Other rare gene mutations including SCN1B have been implicated to BrS. Studying the human cellular phenotype of BrS associated with rare gene mutation remains lacking. Objectives We sought to study the cellular phenotype of BrS with the SCN1B gene variants using human-induced pluripotent stem cell (hiPSCs)–derived cardiomyocytes (hiPSC-CMs). Methods and Results A BrS patient suffering from recurrent syncope harboring a two variants (c.629T \\u0026gt; C and c.637C \\u0026gt; A) in SCN1B, which encodes the function-modifying sodium channel beta1 subunit, and three independent healthy subjects were recruited and their skin biopsies were used to generate hiPSCs, which were differentiated into cardiomyocytes (hiPSC-CMs) for studying the cellular electrophysiology. A significantly reduced peak and late sodium channel current (INa) and a shift of activation curve to more positive potential as well as a shift of inactivation curve to more negative potential were detected in hiPSC-CMs of the BrS patient, indicating that the SCN1B variants impact the function of sodium channels in cardiomyocytes. The reduced INa led to a reduction of amplitude (APA) and upstroke velocity (Vmax) of action potentials. Ajmaline, a sodium channel blocker, showed a stronger effect on APA and Vmax in BrS cells as compared to cells from healthy donors. Furthermore, carbachol was able to increase arrhythmia events and the beating frequency in BrS. Conclusion Our hiPSC-CMs from a BrS-patient with two variants in SCN1B recapitulated some key phenotypic features of BrS and can provide a platform for studies on BrS with SCN1B variants."],["dc.identifier.doi","10.3389/fcell.2019.00261"],["dc.identifier.eissn","2296-634X"],["dc.identifier.pmid","31737628"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/17195"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/78416"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.notes.intern","Merged from goescholar"],["dc.publisher","Frontiers Media S.A."],["dc.relation.eissn","2296-634X"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Studying Brugada Syndrome With an SCN1B Variants in Human-Induced Pluripotent Stem Cell-Derived Cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]