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dc.contributor.advisorHund, Thomas
dc.creatorLane, Cemantha
dc.date.accessioned2020-01-22T21:45:50Z
dc.date.available2020-01-22T21:45:50Z
dc.date.issued2018-05
dc.identifier.urihttp://hdl.handle.net/1811/90833
dc.description.abstractThe heart has evolved elaborate pathways for adapting function to acute stress stimuli [e.g. sympathetic stimulation of β-adrenergic receptors (β-ARs)]. This “fight-or-flight” cardiac response to acute stress involves rapid changes in heart rate and contractility. However, βAR stimulation has been shown to enhance arrhythmogenesis due, in part, to induction of Ca2+ overload in cardiac myoctyes,1,2,3 although the precise mechanism remains unknown. Ca2+/calmodulin-dependent protein kinase II (CaMKII) is activated in response to β adrenergic stimulation and phosphorylates a myriad of intracellular targets including the cardiac sodium channel (Nav1.5) to alter myocyte excitability and Ca2+ handling. Our group and others have shown that CaMKII-dependent phosphorylation of Nav1.5 at Ser571 selectively regulates late sodium current (INa,L) in vivo. CaMKII-dependent increases in INa,L are linked to cardiac dysfunction.4,5,18,19 We hypothesized that CaMKII-dependent phosphorylation of Nav1.5, and subsequent increases in INa,L, are essential for Ca2+ handling defects and acute arrhythmic response to β-AR stimulation. Using optical mapping, we show that CaMKII-dependent phosphorylation of Nav1.5 alters Ca2+ transients and arrhythmia susceptibility at baseline and in response to β-AR agonist isoproterenol. Our data demonstrate an important link between CaMKII-dependent phosphorylation of the Nav1.5 Ser571 site and Ca2+ handling and arrhythmogenesis in response to acute β-AR stimulation.en_US
dc.description.sponsorshipThe Ohio State Universityen_US
dc.language.isoen_USen_US
dc.publisherThe Ohio State Universityen_US
dc.relation.ispartofseriesThe Ohio State University. Department of Biomedical Engineering Honors Theses; 2018en_US
dc.subjectArrhythmiasen_US
dc.subjectOptical Mappingen_US
dc.subjectBeta-adrenergic stimulationen_US
dc.subjectLate sodium currenten_US
dc.subjectCaMKIIen_US
dc.titleThe role of CaMKII-dependent augmented INa,L in arrhythmias during acute β-adrenergic stimulationen_US
dc.typeThesisen_US
dc.description.embargoA one-year embargo was granted for this item.en_US
dc.rights.ccAttribution-NonCommercial-NoDerivs 3.0 United Statesen_US
dc.rights.ccurihttp://creativecommons.org/licenses/by-nc-nd/3.0/us/en_US
dc.description.academicmajorAcademic Major: Biomedical Engineeringen_US


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