Hartmann, Nico Horst

[["dc.bibliographiccitation.journal","European Heart Journal"],["dc.bibliographiccitation.volume","37"],["dc.contributor.author","Hartmann, Nico"],["dc.contributor.author","Pabel, Stefanie Corinna"],["dc.contributor.author","Herting, J. Jonas"],["dc.contributor.author","Schotola, Hanna"],["dc.contributor.author","Fischer, Thomas H."],["dc.contributor.author","Frey, Norbert"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Sossalla, Samuel T."],["dc.date.accessioned","2018-11-07T10:10:28Z"],["dc.date.available","2018-11-07T10:10:28Z"],["dc.date.issued","2016"],["dc.format.extent","720"],["dc.identifier.isi","000383869503395"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/39863"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.publisher.place","Oxford"],["dc.relation.eventlocation","Rome, ITALY"],["dc.relation.issn","1522-9645"],["dc.relation.issn","0195-668X"],["dc.title","Antiarrhythmic effects of dantrolene in human cardiomyocytes from patients with atrial fibrillation or heart failure"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1067"],["dc.bibliographiccitation.journal","European Heart Journal"],["dc.bibliographiccitation.lastpage","1068"],["dc.bibliographiccitation.volume","36"],["dc.contributor.author","Hartmann, Nico"],["dc.contributor.author","Mason, F."],["dc.contributor.author","Braun, I."],["dc.contributor.author","Voigt, Niels"],["dc.contributor.author","Fischer, Thomas H."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Sossalla, Samuel Tobias"],["dc.date.accessioned","2018-11-07T09:53:36Z"],["dc.date.available","2018-11-07T09:53:36Z"],["dc.date.issued","2015"],["dc.identifier.isi","000361205107171"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/36361"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Oxford Univ Press"],["dc.publisher.place","Oxford"],["dc.relation.eventlocation","London, ENGLAND"],["dc.relation.issn","1522-9645"],["dc.relation.issn","0195-668X"],["dc.title","The combined effects of ranolazine and low dose dronedarone on atrial vs. ventricular electrophysiology; a novel therapeutic hope?"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","95"],["dc.bibliographiccitation.journal","Journal of Molecular and Cellular Cardiology"],["dc.bibliographiccitation.lastpage","106"],["dc.bibliographiccitation.volume","94"],["dc.contributor.author","Hartmann, Nico H."],["dc.contributor.author","Mason, Fleur E."],["dc.contributor.author","Braun, Inga"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Voigt, Niels"],["dc.contributor.author","Schotola, Hanna"],["dc.contributor.author","Fischer, Thomas H."],["dc.contributor.author","Dobrev, Dobromir"],["dc.contributor.author","Danner, Bernhard C."],["dc.contributor.author","Renner, André"],["dc.contributor.author","Gummert, Jan"],["dc.contributor.author","Belardinelli, Luiz"],["dc.contributor.author","Frey, Norbert"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2017-09-07T11:44:54Z"],["dc.date.available","2017-09-07T11:44:54Z"],["dc.date.issued","2016"],["dc.description.abstract","Introduction: Pharmacological rhythm control of atrial fibrillation (AF) in patients with structural heart disease is limited. Ranolazine in combination with low dose dronedarone remarkably reduced AF-burden in the phase II HARMONY trial. We thus aimed to investigate the possible mechanisms underlying these results. Methods and results: Patch clamp experiments revealed that ranolazine (5 mu M), low-dose dronedarone (0.3 mu M), and the combination significantly prolonged action potential duration (APD(90)) in atrial myocytes from patients in sinus rhythm (prolongation by 23.5 +/- 0.1%, 31.7 +/- 0.1% and 25.6 +/- 0.1% respectively). Most importantly, in atrial myocytes from patients with AF ranolazine alone, but more the combination with dronedarone, also prolonged the typically abbreviated APD(90) (prolongation by 21.6 +/- 0.1% and 31.9 +/- 0.1% respectively). It was clearly observed that neither ranolazine, dronedarone nor the combination significantly changed the APD or contractility and twitch force in ventricular myocytes or trabeculae from patients with heart failure (HF). Interestingly ranolazine, and more so the combination, but not dronedarone alone, caused hyperpolarization of the resting membrane potential in cardiomyocytes from AF. As measured by confocal microscopy (Fluo-3), ranolazine, dronedarone and the combination significantly suppressed diastolic sarcoplasmic reticulum (SR) Ca2+ leak in myocytes from sinus rhythm (reduction by ranolazine: 89.0 +/- 30.7%, dronedarone: 75.6 +/- 27.4% and combination: 78.0 +/- 272%), in myocytes from AF (reduction by ranolazine: 67.6 +/- 33.7%, dronedarone: 86.5 +/- 31.7% and combination: 81.0 +/- 33.3%), as well as in myocytes from HF (reduction by ranolazine: 64.8 +/- 26.5% and dronedarone: 65.9 +/- 29.3%). Conclusions: Electrophysiological measurements during exposure to ranolazine alone or in combination with low-dose dronedarone showed APD prolongation, cellular hyperpolarization and reduced SR Ca2+ leak in human atrial myocytes. The combined inhibitory effects on various currents, in particular Na+ and K+ currents, may explain the anti-AF effects observed in the HARMONY trial. Therefore, the combination of ranolazine and dronedarone, but also ranolazine alone, may be promising new treatment options for AF, especially in patients with HF, and merit further clinical investigation. (C) 2016 Elsevier Ltd. All rights reserved."],["dc.identifier.doi","10.1016/j.yjmcc.2016.03.012"],["dc.identifier.gro","3141690"],["dc.identifier.isi","000376839000011"],["dc.identifier.pmid","27056421"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/8938"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/146"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation.eissn","1095-8584"],["dc.relation.issn","0022-2828"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.relation.workinggroup","RG T. Fischer"],["dc.relation.workinggroup","RG Voigt (Molecular Pharmacology)"],["dc.title","The combined effects of ranolazine and dronedarone on human atrial and ventricular electrophysiology"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","154"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","ESC Heart Failure"],["dc.bibliographiccitation.lastpage","163"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Ahmad, Shakil"],["dc.contributor.author","Tirilomis, Petros"],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Dybkova, Nataliya"],["dc.contributor.author","Hartmann, Nico"],["dc.contributor.author","Molina, Cristina E."],["dc.contributor.author","Tirilomis, Theodoros"],["dc.contributor.author","Kutschka, Ingo"],["dc.contributor.author","Frey, Norbert"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Streckfuss-Bömeke, Katrin"],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2019-02-26T11:03:53Z"],["dc.date.available","2019-02-26T11:03:53Z"],["dc.date.issued","2019"],["dc.description.abstract","Aims In hypertrophy and heart failure, the proarrhythmic persistent Na+ current (INaL) is enhanced. We aimed to investigate the electrophysiological role of neuronal sodium channel NaV1.8 in human hypertrophied myocardium. Methods and results Myocardial tissue of 24 patients suffering from symptomatic severe aortic stenosis and concomitant significant afterload-induced hypertrophy with preserved ejection fraction was used and compared with 12 healthy controls. We performed quantitative real-time PCR and western blot and detected a significant up-regulation of NaV1.8 mRNA (2.34fold) and protein expression (1.96-fold) in human hypertrophied myocardium compared with healthy hearts. Interestingly, NaV1.5 protein expression was significantly reduced in parallel (0.60-fold). Using whole-cell patch-clamp technique, we found that the prominent INaL was significantly reduced after addition of novel NaV1.8-specific blockers either A-803467 (30 nM) or PF-01247324 (1 μM) in human hypertrophic cardiomyocytes. This clearly demonstrates the relevant contribution of NaV1.8 to this proarrhythmic current. We observed a significant action potential duration shortening and performed confocal microscopy, demonstrating a 50% decrease in proarrhythmic diastolic sarcoplasmic reticulum (SR)-Ca2+ leak and SR-Ca2+ spark frequency after exposure to both NaV1.8 inhibitors."],["dc.identifier.doi","10.1002/ehf2.12378"],["dc.identifier.pmid","30378291"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/57615"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/242"],["dc.language.iso","en"],["dc.notes.status","final"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.rights","CC BY-NC 4.0"],["dc.title","The functional consequences of sodium channel NaV1.8 in human left ventricular hypertrophy"],["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","Der Internist"],["dc.bibliographiccitation.volume","57"],["dc.contributor.author","Herting, J. Jonas"],["dc.contributor.author","Hartmann, Nico"],["dc.contributor.author","Eiringhaus, Joerg"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Sossalla, Samuel T."],["dc.contributor.author","Fischer, T."],["dc.date.accessioned","2018-11-07T10:15:51Z"],["dc.date.available","2018-11-07T10:15:51Z"],["dc.date.issued","2016"],["dc.format.extent","S20"],["dc.identifier.isi","000375417500035"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40900"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","New york"],["dc.relation.issn","1432-1289"],["dc.relation.issn","0020-9554"],["dc.title","Influence of Atrial Fibrillation on the electromechanical Coupling in human Ventricular Myocardium"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","184"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.lastpage","196"],["dc.bibliographiccitation.volume","107"],["dc.contributor.author","Fischer, Thomas H."],["dc.contributor.author","Herting, Jonas"],["dc.contributor.author","Mason, Fleur E."],["dc.contributor.author","Hartmann, Nico"],["dc.contributor.author","Watanabe, Saera"],["dc.contributor.author","Nikolaev, Viacheslav O."],["dc.contributor.author","Sprenger, Julia U."],["dc.contributor.author","Fan, Peidong"],["dc.contributor.author","Yao, Lina"],["dc.contributor.author","Popov, Aron-Frederik"],["dc.contributor.author","Danner, Bernhard C."],["dc.contributor.author","Schoendube, Friedrich"],["dc.contributor.author","Belardinelli, Luiz"],["dc.contributor.author","Hasenfuss, Gerd"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2017-09-07T11:43:42Z"],["dc.date.available","2017-09-07T11:43:42Z"],["dc.date.issued","2015"],["dc.description.abstract","Aims Enhanced cardiac late Na current (late I-Na) and increased sarcoplasmic reticulum (SR)-Ca2+-leak are both highly arrhythmogenic. This study seeks to identify signalling pathways interconnecting late I-Na and SR-Ca2+-leak in atrial cardiomyocytes (CMs). Methods and results In murine atrial CMs, SR-Ca2+-leak was increased by the late I-Na enhancer Anemonia sulcata toxin II (ATX-II). An inhibition of Ca2+/calmodulin-dependent protein kinase II (Autocamide-2-related inhibitory peptide), protein kinase A (H89), or late I-Na (Ranolazine or Tetrodotoxin) all prevented ATX-II-dependent SR-Ca2+-leak. The SR-Ca2+-leak induction by ATX-II was not detected when either the Na+/Ca2+ exchanger was inhibited (KBR) or in CaMKIIdc-knockout mice. FRET measurements revealed increased cAMP levels upon ATX-II stimulation, which could be prevented by inhibition of adenylyl cyclases (ACs) 5 and 6 (NKY 80) but not by inhibition of phosphodiesterases (IBMX), suggesting PKA activation via an AC-dependent increase of cAMP levels. Western blots showed late I-Na-dependent hyperphosphorylation of CaMKII as well as PKA target sites at ryanodine receptor type-2 (-S2814 and -S2808) and phospholamban (-Thr17, -S16). Enhancement of late I-Na did not alter Ca2+-transient amplitude or SR-Ca2+-load. However, upon late I-Na activation and simultaneous CaMKII inhibition, Ca2+-transient amplitude and SR-Ca2+-load were increased, whereas PKA inhibition reduced Ca2+-transient amplitude and load and additionally slowed Ca2+ elimination. In atrial CMs from patients with atrial fibrillation, inhibition of late I-Na, CaMKII, or PKA reduced the SR-Ca2+-leak. Conclusion Late I-Na exerts distinct effects on Ca2+ homeostasis in atrial myocardium through activation of CaMKII and PKA. Inhibition of late I-Na represents a potential approach to attenuate CaMKII activation and decreases SR-Ca2+-leak in atrial rhythm disorders. The interconnection with the cAMP/PKA system further increases the antiarrhythmic potential of late I-Na inhibition."],["dc.identifier.doi","10.1093/cvr/cvv153"],["dc.identifier.gro","3141867"],["dc.identifier.isi","000359088800021"],["dc.identifier.pmid","25990311"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1956"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/104"],["dc.language.iso","en"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A03: Bedeutung CaMKII-abhängiger Mechanismen für die Arrhythmogenese bei Herzinsuffizienz"],["dc.relation.eissn","1755-3245"],["dc.relation.issn","0008-6363"],["dc.relation.issn","1755-3245"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.relation.workinggroup","RG Nikolaev (Cardiovascular Research Center)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.relation.workinggroup","RG T. Fischer"],["dc.title","Late INa increases diastolic SR-Ca2+-leak in atrial myocardium by activating PKA and CaMKII"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","S10"],["dc.bibliographiccitation.journal","Der Internist"],["dc.bibliographiccitation.lastpage","S11"],["dc.bibliographiccitation.volume","57"],["dc.contributor.author","Pabel, Stefanie Corinna"],["dc.contributor.author","Hartmann, Nico"],["dc.contributor.author","Herting, J. Jonas"],["dc.contributor.author","Fischer, T."],["dc.contributor.author","Frey, Norbert"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Sossalla, Samuel T."],["dc.date.accessioned","2018-11-07T10:15:53Z"],["dc.date.available","2018-11-07T10:15:53Z"],["dc.date.issued","2016"],["dc.identifier.isi","000375417500014"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40909"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Springer"],["dc.publisher.place","New york"],["dc.relation.issn","1432-1289"],["dc.relation.issn","0020-9554"],["dc.title","Anti Arrhythmic Effects of Dantrolene in human Heart Failure and in Atrial Fibrillation"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","412"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Heart Rhythm"],["dc.bibliographiccitation.lastpage","419"],["dc.bibliographiccitation.volume","14"],["dc.contributor.author","Hartmann, Nico H."],["dc.contributor.author","Pabel, Steffen"],["dc.contributor.author","Herting, Jonas"],["dc.contributor.author","Schatter, Felix"],["dc.contributor.author","Renner, André"],["dc.contributor.author","Gummert, Jan"],["dc.contributor.author","Schotola, Hanna"],["dc.contributor.author","Danner, Bernhard C."],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Frey, Norbert"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Fischer, Andre"],["dc.contributor.author","Sossalla, Samuel"],["dc.date.accessioned","2017-09-07T11:52:35Z"],["dc.date.available","2017-09-07T11:52:35Z"],["dc.date.issued","2016"],["dc.identifier.doi","10.1016/j.hrthm.2016.09.014"],["dc.identifier.gro","3144963"],["dc.identifier.pmid","27650424"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/2646"],["dc.identifier.url","https://sfb1002.med.uni-goettingen.de/production/literature/publications/300"],["dc.notes.intern","Crossref Import"],["dc.notes.status","public"],["dc.relation","SFB 1002: Modulatorische Einheiten bei Herzinsuffizienz"],["dc.relation","SFB 1002 | A03: Bedeutung CaMKII-abhängiger Mechanismen für die Arrhythmogenese bei Herzinsuffizienz"],["dc.relation","SFB 1002 | D01: Erholung aus der Herzinsuffizienz – Einfluss von Fibrose und Transkriptionssignatur"],["dc.relation.issn","1547-5271"],["dc.relation.workinggroup","RG Hasenfuß (Transition zur Herzinsuffizienz)"],["dc.relation.workinggroup","RG L. Maier (Experimentelle Kardiologie)"],["dc.relation.workinggroup","RG Sossalla (Kardiovaskuläre experimentelle Elektrophysiologie und Bildgebung)"],["dc.relation.workinggroup","RG T. Fischer"],["dc.title","Antiarrhythmic effects of dantrolene in human diseased cardiomyocytes"],["dc.type","journal_article"],["dc.type.internalPublication","unknown"],["dc.type.peerReviewed","no"],["dc.type.subtype","original_ja"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.journal","European Journal of Heart Failure"],["dc.bibliographiccitation.volume","18"],["dc.contributor.author","Herting, J. Jonas"],["dc.contributor.author","Hartmann, Nico"],["dc.contributor.author","Eiringhaus, Joerg"],["dc.contributor.author","Pabel, Stefanie Corinna"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Sossalla, Samuel T."],["dc.contributor.author","Fischer, Thomas H."],["dc.date.accessioned","2018-11-07T10:14:46Z"],["dc.date.available","2018-11-07T10:14:46Z"],["dc.date.issued","2016"],["dc.format.extent","515"],["dc.identifier.isi","000377107504258"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/40681"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Wiley-blackwell"],["dc.publisher.place","Hoboken"],["dc.relation.issn","1879-0844"],["dc.relation.issn","1388-9842"],["dc.title","Effects of atrial fibrillation on ventricular calcium cycling in human myocardium"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.artnumber","33853"],["dc.bibliographiccitation.journal","Scientific Reports"],["dc.bibliographiccitation.volume","6"],["dc.contributor.author","Volland, Cornelia"],["dc.contributor.author","Bremer, Sebastian"],["dc.contributor.author","Hellenkamp, Kristian"],["dc.contributor.author","Hartmann, Nico H."],["dc.contributor.author","Dybkova, Nataliya"],["dc.contributor.author","Khadjeh, Sara"],["dc.contributor.author","Kutschenko, Anna"],["dc.contributor.author","Liebetanz, David"],["dc.contributor.author","Wagner, Stefan"],["dc.contributor.author","Unsoeld, Bernhard W."],["dc.contributor.author","Didie, Michael"],["dc.contributor.author","Toischer, Karl"],["dc.contributor.author","Sossalla, Samuel"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Seidler, Tim"],["dc.date.accessioned","2017-09-07T11:44:37Z"],["dc.date.available","2017-09-07T11:44:37Z"],["dc.date.issued","2016"],["dc.description.abstract","TBC1D10C is a protein previously demonstrated to bind and inhibit Ras and Calcineurin. In cardiomyocytes, also CaMKII is inhibited and all three targeted enzymes are known to promote maladaptive cardiomyocyte hypertrophy. Here, in accordance with lack of Calcineurin inhibition in vivo, we did not observe a relevant anti-hypertrophic effect despite inhibition of Ras and CaMKII. However, cardiomyocyte-specific TBC1D10C overexpressing transgenic mice exhibited enhanced longevity. Ejection fraction and exercise capacity were enhanced in transgenic mice, but shortening of isolated cardiomyocytes was not increased. This suggests longevity resulted from enhanced cardiac performance but independent of cardiomyocyte contractile force. In further search for mechanisms, a transcriptome-wide analysis revealed expressional changes in several genes pertinent to control of heart rate (HR) including Hcn4, Scn10a, Sema3a and Cacna2d2. Indeed, telemetric holter recordings demonstrated slower atrial conduction and significantly lower HR. Pharmacological reduction of HR was previously demonstrated to enhance survival in mice. Thus, in addition to inhibition of stress signaling, TBC1D10C economizes generation of cardiac output via HR reduction, enhancing exercise capacity and survival. TBC1D10C may be a new target for HR reduction and longevity."],["dc.identifier.doi","10.1038/srep33853"],["dc.identifier.gro","3141617"],["dc.identifier.isi","000384478000002"],["dc.identifier.pmid","27667030"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/13792"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/1678"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Nature Publishing Group"],["dc.relation.issn","2045-2322"],["dc.rights","CC BY 4.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/4.0"],["dc.title","Enhanced cardiac TBC1D10C expression lowers heart rate and enhances exercise capacity and survival"],["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"]]