Phosphoinositide 3-kinase gamma controls autonomic regulation of the mouse heart through Gi-independent downregulation of cAMP level.
FEBS Lett
; 579(1): 133-40, 2005 Jan 03.
Article
em En
| MEDLINE
| ID: mdl-15620702
ABSTRACT
Cardiac beta-adrenergic and the muscarinic receptors control contractility and heart rate by triggering multiple signaling events involving downstream targets like the phosphoinositide 3-kinase gamma (PI3Kgamma). We thus investigated whether the lack of PI3Kgamma could play a role in the autonomic regulation of the mouse heart. Contractility and ICaL of mutant cardiac preparations appeared increased in basal conditions and after beta-adrenergic stimulation. However, basal and beta-adrenergic stimulated heart rate were normal. Conversely, muscarinic inhibition of heart rate was reduced without alteration of the Gbetagamma-dependent stimulation of IK,ACh current. In addition, muscarinic-mediated anti-adrenergic effect on papillary muscle contractility and ICaL was significantly depressed. Consistently, cAMP level of PI3Kgamma-null ventricles was always higher than wild-type controls. Thus, PI3Kgamma controls the cardiac function by reducing cAMP concentration independently of Gi-mediated signaling.
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Base de dados:
MEDLINE
Assunto principal:
AMP Cíclico
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Agonistas Adrenérgicos beta
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Antagonistas Muscarínicos
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Fosfatidilinositol 3-Quinases
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Isoenzimas
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Contração Miocárdica
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Miocárdio
Limite:
Animals
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article