Lehnart, Stephan Elmar

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.volume","80"],["dc.contributor.author","Keweloh, B."],["dc.contributor.author","Lehnart, Stephan E."],["dc.contributor.author","Wehling, M."],["dc.contributor.author","Domeier, E."],["dc.contributor.author","Janssen, PML"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.date.accessioned","2018-11-07T09:30:10Z"],["dc.date.available","2018-11-07T09:30:10Z"],["dc.date.issued","2001"],["dc.format.extent","583A"],["dc.identifier.isi","000166692202658"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31236"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Biophysical Society"],["dc.publisher.place","Bethesda"],["dc.relation.issn","0006-3495"],["dc.title","Influence of amino-pyruvate on contractility and cardiac energy metabolism in isolated rabbit myocardial trabeculae"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","829"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Cell"],["dc.bibliographiccitation.lastpage","840"],["dc.bibliographiccitation.volume","113"],["dc.contributor.author","Wehrens, Xander H. T."],["dc.contributor.author","Lehnart, Stephan E."],["dc.contributor.author","Huang, Fannie"],["dc.contributor.author","Vest, John A."],["dc.contributor.author","Reiken, Steven R."],["dc.contributor.author","Mohler, Peter J."],["dc.contributor.author","Sun, Jie"],["dc.contributor.author","Guatimosim, Silvia"],["dc.contributor.author","Song, Long-Sheng"],["dc.contributor.author","Rosemblit, Nora"],["dc.contributor.author","Marks, Andrew R."],["dc.date.accessioned","2022-03-01T11:45:29Z"],["dc.date.available","2022-03-01T11:45:29Z"],["dc.date.issued","2003"],["dc.description.abstract","Arrhythmias, a common cause of sudden cardiac death, can occur in structurally normal hearts, although the mechanism is not known. In cardiac muscle, the ryanodine receptor (RyR2) on the sarcoplasmic reticulum releases the calcium required for muscle contraction. The FK506 binding protein (FKBP12.6) stabilizes RyR2, preventing aberrant activation of the channel during the resting phase of the cardiac cycle. We show that during exercise, RyR2 phosphorylation by cAMP-dependent protein kinase A (PKA) partially dissociates FKBP12.6 from the channel, increasing intracellular Ca2+ release and cardiac contractility. FKBP12.6−/− mice consistently exhibited exercise-induced cardiac ventricular arrhythmias that cause sudden cardiac death. Mutations in RyR2 linked to exercise-induced arrhythmias (in patients with catecholaminergic polymorphic ventricular tachycardia [CPVT]) reduced the affinity of FKBP12.6 for RyR2 and increased single-channel activity under conditions that simulate exercise. These data suggest that “leaky” RyR2 channels can trigger fatal cardiac arrhythmias, providing a possible explanation for CPVT."],["dc.identifier.doi","10.1016/S0092-8674(03)00434-3"],["dc.identifier.gro","3142431"],["dc.identifier.pii","S0092867403004343"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103347"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.notes.status","final"],["dc.relation.issn","0092-8674"],["dc.title","FKBP12.6 Deficiency and Defective Calcium Release Channel (Ryanodine Receptor) Function Linked to Exercise-Induced Sudden Cardiac Death"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","919"],["dc.bibliographiccitation.issue","6"],["dc.bibliographiccitation.journal","The Journal of Cell Biology"],["dc.bibliographiccitation.lastpage","928"],["dc.bibliographiccitation.volume","160"],["dc.contributor.author","Reiken, Steven"],["dc.contributor.author","Lacampagne, Alain"],["dc.contributor.author","Zhou, Hua"],["dc.contributor.author","Kherani, Aftab"],["dc.contributor.author","Lehnart, Stephan Elmar"],["dc.contributor.author","Ward, Chris"],["dc.contributor.author","Huang, Fannie"],["dc.contributor.author","Gaburjakova, Marta"],["dc.contributor.author","Gaburjakova, Jana"],["dc.contributor.author","Rosemblit, Nora"],["dc.contributor.author","Warren, Michelle S."],["dc.contributor.author","He, Kun-lun"],["dc.contributor.author","Yi, Geng-hua"],["dc.contributor.author","Wang, Jie"],["dc.contributor.author","Burkhoff, Daniel"],["dc.contributor.author","Vassort, Guy"],["dc.contributor.author","Marks, Andrew R."],["dc.date.accessioned","2018-04-23T11:48:49Z"],["dc.date.available","2018-04-23T11:48:49Z"],["dc.date.issued","2003"],["dc.description.abstract","The type 1 ryanodine receptor (RyR1) on the sarcoplasmic reticulum (SR) is the major calcium (Ca2+) release channel required for skeletal muscle excitation–contraction (EC) coupling. RyR1 function is modulated by proteins that bind to its large cytoplasmic scaffold domain, including the FK506 binding protein (FKBP12) and PKA. PKA is activated during sympathetic nervous system (SNS) stimulation. We show that PKA phosphorylation of RyR1 at Ser2843 activates the channel by releasing FKBP12. When FKB12 is bound to RyR1, it inhibits the channel by stabilizing its closed state. RyR1 in skeletal muscle from animals with heart failure (HF), a chronic hyperadrenergic state, were PKA hyperphosphorylated, depleted of FKBP12, and exhibited increased activity, suggesting that the channels are “leaky.” RyR1 PKA hyperphosphorylation correlated with impaired SR Ca2+ release and early fatigue in HF skeletal muscle. These findings identify a novel mechanism that regulates RyR1 function via PKA phosphorylation in response to SNS stimulation. PKA hyperphosphorylation of RyR1 may contribute to impaired skeletal muscle function in HF, suggesting that a generalized EC coupling myopathy may play a role in HF."],["dc.identifier.doi","10.1083/jcb.200211012"],["dc.identifier.gro","3142432"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13578"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","0021-9525"],["dc.title","PKA phosphorylation activates the calcium release channel (ryanodine receptor) in skeletal muscle: defective regulation in heart failure"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","12"],["dc.contributor.author","Weninger, Gunnar"],["dc.contributor.author","Pochechueva, Tatiana"],["dc.contributor.author","El Chami, Dana"],["dc.contributor.author","Luo, Xiaojing"],["dc.contributor.author","Kohl, Tobias"],["dc.contributor.author","Brandenburg, Sören"],["dc.contributor.author","Urlaub, Henning"],["dc.contributor.author","Guan, Kaomei"],["dc.contributor.author","Lenz, Christof"],["dc.contributor.author","Lehnart, Stephan Elmar"],["dc.date.accessioned","2022-07-01T07:34:53Z"],["dc.date.available","2022-07-01T07:34:53Z"],["dc.date.issued","2022"],["dc.description.abstract","Calpains are calcium-activated neutral proteases involved in the regulation of key signaling pathways. Junctophilin-2 (JP2) is a Calpain-specific proteolytic target and essential structural protein inside Ca 2+ release units required for excitation-contraction coupling in cardiomyocytes. While downregulation of JP2 by Calpain cleavage in heart failure has been reported, the precise molecular identity of the Calpain cleavage sites and the (patho-)physiological roles of the JP2 proteolytic products remain controversial. We systematically analyzed the JP2 cleavage fragments as function of Calpain-1 versus Calpain-2 proteolytic activities, revealing that both Calpain isoforms preferentially cleave mouse JP2 at R565, but subsequently at three additional secondary Calpain cleavage sites. Moreover, we identified the Calpain-specific primary cleavage products for the first time in human iPSC-derived cardiomyocytes. Knockout of RyR2 in hiPSC-cardiomyocytes destabilized JP2 resulting in an increase of the Calpain-specific cleavage fragments. The primary N-terminal cleavage product NT 1 accumulated in the nucleus of mouse and human cardiomyocytes in a Ca 2+ -dependent manner, closely associated with euchromatic chromosomal regions, where NT 1 is proposed to function as a cardio-protective transcriptional regulator in heart failure. Taken together, our data suggest that stabilizing NT 1 by preventing secondary cleavage events by Calpain and other proteases could be an important therapeutic target for future studies."],["dc.description.sponsorship"," Deutsche Forschungsgemeinschaft http://dx.doi.org/10.13039/501100001659"],["dc.description.sponsorship"," Deutsches Zentrum für Herz-Kreislaufforschung http://dx.doi.org/10.13039/100010447"],["dc.description.sponsorship","Herzzentrum Göttingen"],["dc.description.sponsorship","Open-Access-Publikationsfonds 2022"],["dc.identifier.doi","10.1038/s41598-022-14320-9"],["dc.identifier.pii","14320"],["dc.identifier.pmid","35725601"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/112032"],["dc.identifier.url","https://sfb1190.med.uni-goettingen.de/production/literature/publications/179"],["dc.identifier.url","https://mbexc.uni-goettingen.de/literature/publications/508"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/435"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-581"],["dc.relation","SFB 1190: Transportmaschinen und Kontaktstellen zellulärer Kompartimente"],["dc.relation","SFB 1190 | P03: Erhaltung und funktionelle Kopplung von ER-Kontakten mit der Plasmamembran"],["dc.relation","SFB 1190 | Z02: Massenspektrometrie-basierte Proteomanalyse"],["dc.relation","EXC 2067: Multiscale Bioimaging"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A09: Lokale molekulare Nanodomänen-Regulation der kardialen Ryanodin-Rezeptor-Funktion"],["dc.relation.eissn","2045-2322"],["dc.relation.workinggroup","RG Lehnart (Cellular Biophysics and Translational Cardiology Section)"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Calpain cleavage of Junctophilin-2 generates a spectrum of calcium-dependent cleavage products and DNA-rich NT1-fragment domains in cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1403"],["dc.bibliographiccitation.issue","11"],["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.lastpage","1417"],["dc.bibliographiccitation.volume","113"],["dc.contributor.author","Tzimas, Christos"],["dc.contributor.author","Johnson, Daniel M."],["dc.contributor.author","Santiago, Demetrio J."],["dc.contributor.author","Vafiadaki, Elizabeth"],["dc.contributor.author","Arvanitis, Demetrios A."],["dc.contributor.author","Davos, Constantinos H."],["dc.contributor.author","Varela, Aimilia"],["dc.contributor.author","Athanasiadis, Nikolaos C."],["dc.contributor.author","Dimitriou, Constantinos"],["dc.contributor.author","Katsimpoulas, Michalis"],["dc.contributor.author","Sonntag, Stephan"],["dc.contributor.author","Kryzhanovska, Mariya"],["dc.contributor.author","Shmerling, Doron"],["dc.contributor.author","Lehnart, Stephan Elmar"],["dc.contributor.author","Sipido, Karin R."],["dc.contributor.author","Kranias, Evangelia G."],["dc.contributor.author","Sanoudou, Despina"],["dc.date.accessioned","2018-05-07T09:40:59Z"],["dc.date.available","2018-05-07T09:40:59Z"],["dc.date.issued","2017"],["dc.description.abstract","The histidine-rich calcium-binding protein (HRC) Ser96Ala variant has previously been identified as a potential biomarker for ventricular arrhythmias and sudden cardiac death in patients with idiopathic dilated cardiomyopathy. Herein, the role of this variant in cardiac pathophysiology is delineated through a novel mouse model, carrying the human mutation in the homologous mouse position."],["dc.identifier.doi","10.1093/cvr/cvx113"],["dc.identifier.pmid","28859293"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/14610"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation.doi","10.1093/cvr/cvx113"],["dc.relation.eissn","1755-3245"],["dc.relation.issn","1755-3245"],["dc.title","Impaired calcium homeostasis is associated with sudden cardiac death and arrhythmias in a genetic equivalent mouse model of the human HRC-Ser96Ala variant"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","318a"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Biophysical Journal"],["dc.bibliographiccitation.volume","106"],["dc.contributor.author","Walker, Mark A."],["dc.contributor.author","Williams, George S. B."],["dc.contributor.author","Kohl, Tobias"],["dc.contributor.author","Jafri, Saleet"],["dc.contributor.author","Lehnart, Stephan E."],["dc.contributor.author","Greenstein, Joseph L."],["dc.contributor.author","Lederer, W. J."],["dc.contributor.author","Winslow, Raimond L."],["dc.date.accessioned","2022-03-01T11:44:58Z"],["dc.date.available","2022-03-01T11:44:58Z"],["dc.date.issued","2014"],["dc.identifier.doi","10.1016/j.bpj.2013.11.1839"],["dc.identifier.pii","S000634951303097X"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/103175"],["dc.language.iso","en"],["dc.notes.intern","DOI-Import GROB-531"],["dc.relation.issn","0006-3495"],["dc.title","Super-Resolution Modeling of Calcium Release in Heart"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","102"],["dc.bibliographiccitation.journal","International Journal of Cardiology"],["dc.bibliographiccitation.lastpage","107"],["dc.bibliographiccitation.volume","272"],["dc.contributor.author","Bergau, Leonard"],["dc.contributor.author","Willems, Rik"],["dc.contributor.author","Sprenkeler, David J."],["dc.contributor.author","Fischer, Thomas H."],["dc.contributor.author","Flevari, Panayota"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Katsaras, Dimitrios"],["dc.contributor.author","Kirova, Aleksandra"],["dc.contributor.author","Lehnart, Stephan E."],["dc.contributor.author","Lüthje, Lars"],["dc.contributor.author","Röver, Christian"],["dc.contributor.author","Seegers, Joachim"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Dunnink, Albert"],["dc.contributor.author","Sritharan, Rajevaa"],["dc.contributor.author","Tuinenburg, Anton E."],["dc.contributor.author","Vandenberk, Bert"],["dc.contributor.author","Vos, Marc A."],["dc.contributor.author","Wijers, Sofieke C."],["dc.contributor.author","Friede, Tim"],["dc.contributor.author","Zabel, Markus"],["dc.date.accessioned","2019-07-09T11:50:23Z"],["dc.date.available","2019-07-09T11:50:23Z"],["dc.date.issued","2018"],["dc.description.abstract","BACKGROUND AND OBJECTIVE: We prospectively investigated combinations of risk stratifiers including multiple EP diagnostics in a cohort study of ICD patients. METHODS: For 672 enrolled patients, we collected history, LVEF, EP study and T-wave alternans testing, 24-h Holter, NT-proBNP, and the eGFR. All-cause mortality and first appropriate ICD shock were predefined endpoints. RESULTS: The 635 patients included in the final analyses were 63 ± 13 years old, 81% were male, LVEF averaged 40 ± 14%, 20% were inducible at EP study, 63% had a primary prophylactic ICD. During follow-up over 4.3 ± 1.5 years, 108 patients died (4.0% per year), and appropriate shock therapy occurred in n = 96 (3.9% per year). In multivariate regression, age (p < 0.001), LVEF (p < 0.001), NYHA functional class (p = 0.007), eGFR (p = 0.024), a history of atrial fibrillation (p = 0.011), and NT-pro-BNP (p = 0.002) were predictors of mortality. LVEF (p = 0.002), inducibility at EP study (p = 0.007), and secondary prophylaxis (p = 0.002) were identified as independent predictors of appropriate shocks. A high annualized risk of shocks of about 10% per year was prevalent in the upper quintile of the shock score. In contrast, a low annual risk of shocks (1.8% per year) was found in the lower two quintiles of the shock score. The lower two quintiles of the mortality score featured an annual mortality <0.6%. CONCLUSIONS: In a prospective ICD patient cohort, a very good approximation of mortality versus arrhythmic risk was possible using a multivariable diagnostic strategy. EP stimulation is the best test to assess risk of arrhythmias resulting in ICD shocks."],["dc.identifier.doi","10.1016/j.ijcard.2018.06.103"],["dc.identifier.pmid","29983251"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/15929"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/59764"],["dc.language.iso","en"],["dc.notes.intern","Merged from goescholar"],["dc.notes.intern","In goescholar not merged with http://resolver.sub.uni-goettingen.de/purl?gs-1/15360 but duplicate"],["dc.relation","info:eu-repo/grantAgreement/EC/FP7/241526/EU//EUTRIGTREAT"],["dc.relation.issn","1874-1754"],["dc.rights","CC BY-NC-ND 4.0"],["dc.rights.access","openAccess"],["dc.rights.uri","https://creativecommons.org/licenses/by-nc-nd/4.0"],["dc.subject.ddc","610"],["dc.subject.mesh","Aged"],["dc.subject.mesh","Aged, 80 and over"],["dc.subject.mesh","Arrhythmias, Cardiac"],["dc.subject.mesh","Cohort Studies"],["dc.subject.mesh","Death, Sudden, Cardiac"],["dc.subject.mesh","Defibrillators"],["dc.subject.mesh","Defibrillators, Implantable"],["dc.subject.mesh","Female"],["dc.subject.mesh","Follow-Up Studies"],["dc.subject.mesh","Humans"],["dc.subject.mesh","Male"],["dc.subject.mesh","Middle Aged"],["dc.subject.mesh","Mortality"],["dc.subject.mesh","Multivariate Analysis"],["dc.subject.mesh","Natriuretic Peptide, Brain"],["dc.subject.mesh","Peptide Fragments"],["dc.subject.mesh","Prospective Studies"],["dc.subject.mesh","Risk Factors"],["dc.title","Differential multivariable risk prediction of appropriate shock versus competing mortality - A prospective cohort study to estimate benefits from ICD therapy"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","416"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","EP Europace"],["dc.bibliographiccitation.lastpage","422"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Seegers, Joachim"],["dc.contributor.author","Vos, Marc A."],["dc.contributor.author","Flevari, Panagiota"],["dc.contributor.author","Willems, Rik"],["dc.contributor.author","Sohns, Christian"],["dc.contributor.author","Vollmann, Dirk"],["dc.contributor.author","Luethje, Lars"],["dc.contributor.author","Kremastinos, Dimitrios T."],["dc.contributor.author","Flore, Vincent"],["dc.contributor.author","Meine, Mathias"],["dc.contributor.author","Tuinenburg, Anton"],["dc.contributor.author","Myles, Rachel C."],["dc.contributor.author","Simon, Dirk"],["dc.contributor.author","Brockmöller, Jürgen"],["dc.contributor.author","Friede, Tim"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Lehnart, Stephan E."],["dc.contributor.author","Zabel, Markus"],["dc.date.accessioned","2017-09-07T11:48:57Z"],["dc.date.available","2017-09-07T11:48:57Z"],["dc.date.issued","2012"],["dc.description.abstract","Aims The EUTrigTreat clinical study has been designed as a prospective multicentre observational study and aims to (i) risk stratify patients with an implantable cardioverter defibrillator (ICD) for mortality and shock risk using multiple novel and established risk markers, (ii) explore a link between repolarization biomarkers and genetics of ion (Ca-2, Na, K) metabolism, (iii) compare the results of invasive and non-invasive electrophysiological (EP) testing, (iv) assess changes of non-invasive risk stratification tests over time, and (v) associate arrythmogenomic risk through 19 candidate genes. Methods and results Patients with clinical ICD indication are eligible for the trial. Upon inclusion, patients will undergo non-invasive risk stratification, including beat-to-beat variability of repolarization (BVR), T-wave alternans, T-wave morphology variables, ambient arrhythmias from Holter, heart rate variability, and heart rate turbulence. Non-invasive or invasive programmed electrical stimulation will assess inducibility of ventricular arrhythmias, with the latter including recordings of monophasic action potentials and assessment of restitution properties. Established candidate genes are screened for variants. The primary endpoint is all-cause mortality, while one of the secondary endpoints is ICD shock risk. A mean follow-up of 3.3 years is anticipated. Non-invasive testing will be repeated annually during follow-up. It has been calculated that 700 patients are required to identify risk predictors of the primary endpoint, with a possible increase to 1000 patients based on interim risk analysis. Conclusion The EUTrigTreat clinical study aims to overcome current shortcomings in sudden cardiac death risk stratification and to answer several related research questions. The initial patient recruitment is expected to be completed in July 2012, and follow-up is expected to end in September 2014. Clinicaltrials.gov identifier: NCT01209494."],["dc.identifier.doi","10.1093/europace/eur352"],["dc.identifier.gro","3142572"],["dc.identifier.isi","000300717700021"],["dc.identifier.pmid","22117037"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7031"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8937"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: European Community [HEALTH-F2-2009-241526, EUTrigTreat]"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1099-5129"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Rationale, objectives, and design of the EUTrigTreat clinical study: a prospective observational study for arrhythmia risk stratification and assessment of interrelationships among repolarization markers and genotype"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","2325"],["dc.bibliographiccitation.issue","20"],["dc.bibliographiccitation.journal","Circulation"],["dc.bibliographiccitation.lastpage","2345"],["dc.bibliographiccitation.volume","116"],["dc.contributor.author","Lehnart, Stephan Elmar"],["dc.contributor.author","Ackerman, Michael J."],["dc.contributor.author","Benson, D. Woodrow"],["dc.contributor.author","Brugada, Ramon"],["dc.contributor.author","Clancy, Colleen"],["dc.contributor.author","Donahue, J. Kevin"],["dc.contributor.author","George, Alfred L."],["dc.contributor.author","Grant, Augustus O."],["dc.contributor.author","Groft, Stephen C."],["dc.contributor.author","January, Craig T."],["dc.contributor.author","Lathrop, David A."],["dc.contributor.author","Lederer, W. Jonathan"],["dc.contributor.author","Makielski, Jonathan C."],["dc.contributor.author","Mohler, Peter J."],["dc.contributor.author","Moss, Arthur"],["dc.contributor.author","Nerbonne, Jeanne M."],["dc.contributor.author","Olson, Timothy M."],["dc.contributor.author","Przywara, Dennis A."],["dc.contributor.author","Towbin, Jeffrey A."],["dc.contributor.author","Wang, Lan-Hsiang"],["dc.contributor.author","Marks, Andrew R."],["dc.date.accessioned","2018-05-09T14:00:10Z"],["dc.date.available","2018-05-09T14:00:10Z"],["dc.date.issued","2007"],["dc.description.abstract","The National Heart, Lung, and Blood Institute and Office of Rare Diseases at the National Institutes of Health organized a workshop (September 14 to 15, 2006, in Bethesda, Md) to advise on new research directions needed for improved identification and treatment of rare inherited arrhythmias. These included the following: (1) Na+ channelopathies; (2) arrhythmias due to K+ channel mutations; and (3) arrhythmias due to other inherited arrhythmogenic mechanisms. Another major goal was to provide recommendations to support, enable, or facilitate research to improve future diagnosis and management of inherited arrhythmias. Classifications of electric heart diseases have proved to be exceedingly complex and in many respects contradictory. A new contemporary and rigorous classification of arrhythmogenic cardiomyopathies is proposed. This consensus report provides an important framework and overview to this increasingly heterogeneous group of primary cardiac membrane channel diseases. Of particular note, the present classification scheme recognizes the rapid evolution of molecular biology and novel therapeutic approaches in cardiology, as well as the introduction of many recently described diseases, and is unique in that it incorporates ion channelopathies as a primary cardiomyopathy in consensus with a recent American Heart Association Scientific Statement."],["dc.identifier.gro","3142414"],["dc.identifier.pmid","17998470"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13558"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.status","final"],["dc.relation.doi","10.1161/CIRCULATIONAHA.107.711689"],["dc.relation.eissn","1524-4539"],["dc.relation.issn","1524-4539"],["dc.relation.issn","0009-7322"],["dc.title","Inherited arrhythmias: a National Heart, Lung, and Blood Institute and Office of Rare Diseases workshop consensus report about the diagnosis, phenotyping, molecular mechanisms, and therapeutic approaches for primary cardiomyopathies of gene mutations affecting ion channel function"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","7906"],["dc.bibliographiccitation.issue","20"],["dc.bibliographiccitation.journal","Proceedings of the National Academy of Sciences"],["dc.bibliographiccitation.lastpage","7910"],["dc.bibliographiccitation.volume","103"],["dc.contributor.author","Lehnart, Stephan Elmar"],["dc.contributor.author","Terrenoire, Cecile"],["dc.contributor.author","Reiken, Steven"],["dc.contributor.author","Wehrens, Xander H. T."],["dc.contributor.author","Song, Long-Sheng"],["dc.contributor.author","Tillman, Erik J."],["dc.contributor.author","Mancarella, Salvatore"],["dc.contributor.author","Coromilas, James"],["dc.contributor.author","Lederer, W. J."],["dc.contributor.author","Kass, Robert S."],["dc.contributor.author","Marks, Andrew R."],["dc.date.accessioned","2018-04-23T11:48:42Z"],["dc.date.available","2018-04-23T11:48:42Z"],["dc.date.issued","2006"],["dc.description.abstract","Catecholaminergic polymorphic ventricular tachycardia is a form of exercise-induced sudden cardiac death that has been linked to mutations in the cardiac Ca2+ release channel/ryanodine receptor (RyR2) located on the sarcoplasmic reticulum (SR). We have shown that catecholaminergic polymorphic ventricular tachycardia-linked RyR2 mutations significantly decrease the binding affinity for calstabin-2 (FKBP12.6), a subunit that stabilizes the closed state of the channel. We have proposed that RyR2-mediated diastolic SR Ca2+ leak triggers ventricular tachycardia (VT) and sudden cardiac death. In calstabin-2-deficient mice, we have now documented diastolic SR Ca2+ leak, monophasic action potential alternans, and bidirectional VT. Calstabin-deficient cardiomyocytes exhibited SR Ca2+ leak-induced aberrant transient inward currents in diastole consistent with delayed after-depolarizations. The 1,4-benzothiazepine JTV519, which increases the binding affinity of calstabin-2 for RyR2, inhibited the diastolic SR Ca2+ leak, monophasic action potential alternans and triggered arrhythmias. Our data suggest that calstabin-2 deficiency is as a critical mediator of triggers that initiate cardiac arrhythmias."],["dc.identifier.doi","10.1073/pnas.0602133103"],["dc.identifier.gro","3142418"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/13562"],["dc.language.iso","en"],["dc.notes.intern","lifescience updates Crossref Import"],["dc.notes.status","final"],["dc.relation.issn","0027-8424"],["dc.title","Stabilization of cardiac ryanodine receptor prevents intracellular calcium leak and arrhythmias"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dspace.entity.type","Publication"]]