Linked Life Data

19629520

Source:http://linkedlifedata.com/resource/pubmed/id/19629520

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2009-9-17
pubmed:abstractText
Thyroid hormone (TH) markedly modulates cardiovascular function and heart rate. The pacemaker current I(f) and encoding hyperpolarization-activated cation (HCN) genes have been identified as TH targets. To analyze the specific contribution and functional significance of thyroid receptor isoforms responsible for HCN gene transactivation, we generated transgenic neonatal rat cardiomyocytes with adenovirus-mediated overexpression of the thyroid receptors alpha1 (TR alpha 1) and beta1 (TR beta 1), and analyzed native I(f) current and expression levels of the underlying molecular components HCN2 and HCN4. Initial results revealed that spontaneous beating activity was higher in TR alpha 1- and lower in TR beta 1-expressing cardiomyocytes. This was associated with accelerated depolarization velocity and abbreviated action potential duration in cells overexpressing TR alpha 1, while TR beta 1 suppressed phase 4 depolarization and prolonged action potentials. Consistently, TR alpha 1-infected myocytes exhibited larger I(f) current densities along with increased HCN2 and HCN4 mRNA and protein levels. In contrast, HCN2 gene expression was not significantly affected by TR beta 1. TR beta 1 exclusively suppressed HCN4 transcription. T3 application led to significant effects only in controls and TR alpha 1-infected cardiomyocytes; whereas, no ligand-dependent actions were observed in TR beta 1-expressing neonatal cardiomyocytes. Our results demonstrate that TR alpha 1 and TR beta 1 divergently regulate cardiac pacing activity. TH-induced positive chronotropic effects are likely to be mediated by TR alpha 1 through enhanced expression of I(f) pacemaker current and its underlying genes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1432-2013
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
458
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1061-8
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Distinct regulation of cardiac I(f) current via thyroid receptors alpha1 and beta1.
pubmed:affiliation
Department of Internal Medicine III, University of Cologne, Kerpener Str. 62, 50937, Cologne, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't