Loss of cardiac phosphoinositide 3-kinase p110 alpha results in contractile dysfunction.
Circulation
; 120(4): 318-25, 2009 Jul 28.
Article
em En
| MEDLINE
| ID: mdl-19597047
ABSTRACT
BACKGROUND:
Phosphoinositide 3-kinase (PI3K) p110alpha plays a key role in insulin action and tumorigenesis. Myocyte contraction is initiated by an inward Ca(2+) current (I(Ca,L)) through the voltage-dependent L-type Ca(2+) channel (LTCC). The aim of this study was to evaluate whether p110alpha also controls cardiac contractility by regulating the LTCC. METHODS ANDRESULTS:
Genetic ablation of p110alpha (also known as Pik3ca), but not p110beta (also known as Pik3cb), in cardiac myocytes of adult mice reduced I(Ca,L) and blocked insulin signaling in the heart. p110alpha-null myocytes had a reduced number of LTCCs on the cell surface and a contractile defect that decreased cardiac function in vivo. Similarly, pharmacological inhibition of p110alpha decreased I(Ca,L) and contractility in canine myocytes. Inhibition of p110beta did not reduce I(Ca,L).CONCLUSIONS:
PI3K p110alpha but not p110beta regulates the LTCC in cardiac myocytes. Decreased signaling to p110alpha reduces the number of LTCCs on the cell surface and thus attenuates I(Ca,L) and contractility.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fosfatidilinositol 3-Quinases
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Miócitos Cardíacos
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Contração Miocárdica
Limite:
Animals
Idioma:
En
Revista:
Circulation
Ano de publicação:
2009
Tipo de documento:
Article
País de afiliação:
Estados Unidos