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http://purl.uniprot.org/citations/15520314http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/15520314http://www.w3.org/2000/01/rdf-schema#comment"

Background

Conduction system defects and slowed ventricular conduction are common in patients with systolic dysfunction and contribute to arrhythmias and sudden death. In animal models of heart failure, cardiac alpha1-adrenergic signaling is constitutively activated. Here, we report the effects of constitutive activation of alpha1-adrenergic signaling on connexin phosphorylation and cardiac conduction.

Methods and results

Transgenic mice were generated with cardiac-specific overexpression of the transcription factor RTEF-1 (transcription enhancer factor-1-related factor), which mediates alpha1-adrenergic signaling in cardiac myocytes. Surface and intracardiac ECGs revealed prolongation of the PR, QRS, and AH intervals and the appearance of progressive atrial arrhythmias in RTEF-1 mice. Optical mapping using voltage-sensitive dye revealed slower conduction velocities across the atrial and ventricular myocardium. Intercellular dye transfer between RTEF-1 transgenic cardiac myocytes confirmed impaired conduction at the cellular level. Conduction defects were correlated with dephosphorylation of connexin40 and connexin43 and upregulation of protein phosphatase 1beta (PP1beta). Overexpression of PP1beta in HeLa cells dephosphorylated cardiac connexin. Confocal microscopy revealed increased levels of dephosphorylated connexin43 at the cardiac gap junctions in RTEF-1 mice, suggesting that defective conduction is a result of impaired gap-junction conductance rather than assembly.

Conclusions

Constitutive activation of alpha1-adrenergic signaling through the RTEF-1 transcription factor results in chronic elevation of PP1beta expression and connexin dephosphorylation. This mechanism may underlie some defects in cardiac conduction."xsd:string
http://purl.uniprot.org/citations/15520314http://purl.org/dc/terms/identifier"doi:10.1161/01.cir.0000146902.84099.26"xsd:string
http://purl.uniprot.org/citations/15520314http://purl.uniprot.org/core/author"Maeda T."xsd:string
http://purl.uniprot.org/citations/15520314http://purl.uniprot.org/core/author"Chen H.H."xsd:string
http://purl.uniprot.org/citations/15520314http://purl.uniprot.org/core/author"Stewart A.F."xsd:string
http://purl.uniprot.org/citations/15520314http://purl.uniprot.org/core/author"Ueyama T."xsd:string
http://purl.uniprot.org/citations/15520314http://purl.uniprot.org/core/author"Brooks S."xsd:string
http://purl.uniprot.org/citations/15520314http://purl.uniprot.org/core/author"London B."xsd:string
http://purl.uniprot.org/citations/15520314http://purl.uniprot.org/core/author"Baty C.J."xsd:string
http://purl.uniprot.org/citations/15520314http://purl.uniprot.org/core/author"Salama G."xsd:string
http://purl.uniprot.org/citations/15520314http://purl.uniprot.org/core/author"Saba S."xsd:string
http://purl.uniprot.org/citations/15520314http://purl.uniprot.org/core/author"Gursoy E."xsd:string
http://purl.uniprot.org/citations/15520314http://purl.uniprot.org/core/author"Baker L.C."xsd:string
http://purl.uniprot.org/citations/15520314http://purl.uniprot.org/core/date"2004"xsd:gYear
http://purl.uniprot.org/citations/15520314http://purl.uniprot.org/core/name"Circulation"xsd:string
http://purl.uniprot.org/citations/15520314http://purl.uniprot.org/core/pages"2980-2987"xsd:string
http://purl.uniprot.org/citations/15520314http://purl.uniprot.org/core/title"Transcription enhancer factor-1-related factor-transgenic mice develop cardiac conduction defects associated with altered connexin phosphorylation."xsd:string
http://purl.uniprot.org/citations/15520314http://purl.uniprot.org/core/volume"110"xsd:string
http://purl.uniprot.org/citations/15520314http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/15520314
http://purl.uniprot.org/citations/15520314http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/15520314
http://purl.uniprot.org/uniprot/#_Q15561-mappedCitation-15520314http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15520314
http://purl.uniprot.org/uniprot/#_A0A0S2Z4E5-mappedCitation-15520314http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15520314
http://purl.uniprot.org/uniprot/#_A0A0S2Z4F2-mappedCitation-15520314http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15520314
http://purl.uniprot.org/uniprot/#_D3DUQ6-mappedCitation-15520314http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/15520314
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