Linked Life Data

16627784

Source:http://linkedlifedata.com/resource/pubmed/id/16627784

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2006-6-9
pubmed:abstractText
Ca2+ influx through the L-type Ca2+ channel (I(Ca,L)) is a key determinant of cardiac contractility and is modulated by multiple signaling pathways. Because the regulation of I(Ca,L) by phosphoinositide-3-kinases (PI3Ks) and phosphoinositide-3-phosphatase (PTEN) is unknown, despite their involvement in the regulation of myocardial growth and contractility, I(Ca,L) was recorded in myocytes isolated from mice overexpressing a dominant-negative p110alpha mutant (DN-p110alpha) in the heart, lacking the PI3Kgamma gene (PI3Kgamma(-/-)) or with muscle-specific ablation of PTEN (PTEN(-/-)). Combinations of these genetically altered mice were also examined. Although there were no differences in the expression level of CaV1.2 proteins, basal I(Ca,L) densities were larger (P<0.01) in PTEN(-/-) myocytes compared with littermate controls, PI3Kgamma(-/-), or DN-p110alpha myocytes and showed negative shifts in voltage dependence of current activation. The I(Ca,L) differences seen in PTEN(-/-) mice were eliminated by pharmacological inhibition of either PI3Ks or protein kinase B (PKB) as well as in PTEN(-/-)/DN-p110alpha double mutant mice but not in PTEN(-/-)/PI3Kgamma(-/-) mice. On the other hand, application of insulin-like growth factor-1 (IGF-1), an activator of PKB, increased I(Ca,L) in control and PI3Kgamma(-/-), while having no effects on I(Ca,L) in DN-p110alpha or PTEN(-/-) mice. The I(Ca,L) increases induced by IGF-1 were abolished by PKB inhibition. Our results demonstrate that IGF-1 treatment or inactivation of PTEN enhances I(Ca,L) via PI3Kalpha-dependent increase in PKB activation.
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
9
pubmed:volume
98
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1390-7
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Insulin-like growth factor-1 and PTEN deletion enhance cardiac L-type Ca2+ currents via increased PI3Kalpha/PKB signaling.
pubmed:affiliation
Department of Physiology, University Health Network, University of Toronto, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't