Lehnart, Stephan Elmar

[["dc.bibliographiccitation.firstpage","4388"],["dc.bibliographiccitation.issue","12"],["dc.bibliographiccitation.journal","Journal of Clinical Investigation"],["dc.bibliographiccitation.lastpage","4398"],["dc.bibliographiccitation.volume","120"],["dc.contributor.author","Shan, Jian"],["dc.contributor.author","Kushnir, Alexander"],["dc.contributor.author","Betzenhauser, Matthew J."],["dc.contributor.author","Reiken, Steven"],["dc.contributor.author","Li, Jingdong"],["dc.contributor.author","Lindegger, Nicolas"],["dc.contributor.author","Mongillo, Marco"],["dc.contributor.author","Mohler, Peter J."],["dc.contributor.author","Marks, Andrew R."],["dc.contributor.author","Lehnart, Stephan E."],["dc.date.accessioned","2021-11-22T14:31:51Z"],["dc.date.available","2021-11-22T14:31:51Z"],["dc.date.issued","2010"],["dc.description.abstract","During the classic “fight-or-flight” stress response, sympathetic nervous system activation leads to catecholamine release, which increases heart rate and contractility, resulting in enhanced cardiac output. Catecholamines bind to β-adrenergic receptors, causing cAMP generation and activation of PKA, which phosphorylates multiple targets in cardiac muscle, including the cardiac ryanodine receptor/calcium release channel (RyR2) required for muscle contraction. PKA phosphorylation of RyR2 enhances channel activity by sensitizing the channel to cytosolic calcium (Ca2+). Here, we found that mice harboring RyR2 channels that cannot be PKA phosphorylated (referred to herein as RyR2-S2808A+/+ mice) exhibited blunted heart rate and cardiac contractile responses to catecholamines (isoproterenol). The isoproterenol-induced enhancement of ventricular myocyte Ca2+ transients and fractional shortening (contraction) and the spontaneous beating rate of sinoatrial nodal cells were all blunted in RyR2-S2808A+/+ mice. The blunted cardiac response to catecholamines in RyR2-S2808A+/+ mice resulted in impaired exercise capacity. RyR2-S2808A+/+ mice were protected against chronic catecholaminergic-induced cardiac dysfunction. These studies identify what we believe to be new roles for PKA phosphorylation of RyR2 in both the heart rate and contractile responses to acute catecholaminergic stimulation."],["dc.identifier.doi","10.1172/JCI32726"],["dc.identifier.fs","576355"],["dc.identifier.gro","3142407"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/7564"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/93408"],["dc.language.iso","en"],["dc.notes.intern","Migrated from goescholar"],["dc.notes.status","final"],["dc.relation.doi","10.1172/JCI32726"],["dc.relation.eissn","1558-8238"],["dc.relation.issn","0021-9738"],["dc.relation.issn","1558-8238"],["dc.rights.access","openAccess"],["dc.subject","fight-or-flight stress response; β-AR stimulation"],["dc.title","Phosphorylation of the ryanodine receptor mediates the cardiac fight or flight response in mice"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]