Unknown

Dataset Information

0

Loss of cardiac phosphoinositide 3-kinase p110 alpha results in contractile dysfunction.


ABSTRACT: 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.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).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.

SUBMITTER: Lu Z 

PROVIDER: S-EPMC2734096 | biostudies-literature | 2009 Jul

REPOSITORIES: biostudies-literature

altmetric image

Publications

Loss of cardiac phosphoinositide 3-kinase p110 alpha results in contractile dysfunction.

Lu Zhongju Z   Jiang Ya-Ping YP   Wang Wei W   Xu Xin-Hua XH   Mathias Richard T RT   Entcheva Emilia E   Ballou Lisa M LM   Cohen Ira S IS   Lin Richard Z RZ  

Circulation 20090713 4


<h4>Background</h4>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.<h4>Methods and results</h4>Genetic ablation of p110alpha (also known as Pik3ca), but not p110beta (also known as Pik3cb), in cardiac myoc  ...[more]

Similar Datasets

| S-EPMC2807342 | biostudies-literature
| S-EPMC6321576 | biostudies-literature
| S-EPMC3581375 | biostudies-literature
| S-EPMC3216328 | biostudies-literature
2012-12-01 | E-GEOD-40564 | biostudies-arrayexpress
| S-EPMC5415238 | biostudies-literature
| S-EPMC7695136 | biostudies-literature
| S-EPMC6719401 | biostudies-literature
2003-07-24 | GSE558 | GEO
| S-EPMC2967619 | biostudies-literature