Linked Life Data

18303085

Source:http://linkedlifedata.com/resource/pubmed/id/18303085

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2008-4-23
pubmed:abstractText
Congenital heart defects (CHD) are common in Down syndrome (DS, trisomy 21). Recently, cardiac sympathetic-parasympathetic imbalance has also been documented in DS adults free of any CHD. The KCNJ6 gene located on human chromosome 21 encodes for the Kir3.2/GIRK2 protein subunits of G protein-regulated K(+) (K(G)) channels and could contribute to this altered cardiac regulation. To elucidate the role of its overexpression, we used homozygous transgenic (Tg(+/+)) mice carrying copies of human KCNJ6. These mice showed human Kir3.2 mRNA expression in the heart and a 2.5-fold increased translation in the atria. Phenotypic alterations were assessed by recording electrocardiogram of urethane anesthetized mice. Chronotropic responses to direct (carbachol) and indirect (methoxamine) muscarinic stimulation were enhanced in Tg(+/+) mice with respect to wild-type (WT) mice. Alternating periods of slow and fast rhythm induced by CCPA (2-chloro-N-cyclopentyl-adenosine) were amplified in Tg(+/+) mice, resulting in a reduced negative chronotropic effect. These drugs reduced the atrial P wave amplitude and area. P wave variations induced by methoxamine and CCPA were respectively increased and reduced in the Tg(+/+) mice, while PR interval and ventricular wave showed no difference between Tg(+/+) and WT. These results indicate that Tg(+/+) mice incorporating the human KCNJ6 exhibit altered Kir3.2 expression and responses to drugs that would activate K(G) channels. Moreover, these altered expression and responses are limited to sino-atrial node and atria that normally express large amounts of K(G) channels. These data suggest that KCNJ6 could play an important role in altered cardiac regulation in DS patients.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1531-2267
pubmed:author
pubmed:issnType
Electronic
pubmed:day
22
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
230-9
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Altered heart rate control in transgenic mice carrying the KCNJ6 gene of the human chromosome 21.
pubmed:affiliation
Centre National de la Recherche Scientifique Unité Mixte de Recherche 6542, Physiologie des Cellules Cardiaques et Vasculaires, Université François-Rabelais, Parc Grandmont, Tours, France. jacques.lignon@univ-tours.fr
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't