title: Loss of cardiac phosphoinositide 3-kinase p110 alpha results in contractile dysfunction.
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.
  
  
  RESULTS
  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.
authors: Department of Physiology and Biophysics, Stony Brook University, Stony Brook, NY 11794-8151, USA.
authors: Zhongju
authors: Z
authors: Lu
authors: Ya-Ping
authors: YP
authors: Jiang
authors: Wei
authors: W
authors: Wang
authors: Xin-Hua
authors: XH
authors: Xu
authors: Richard T
authors: RT
authors: Mathias
authors: Emilia
authors: E
authors: Entcheva
authors: Lisa M
authors: LM
authors: Ballou
authors: Ira S
authors: IS
authors: Cohen
authors: Richard Z
authors: RZ
authors: Lin
mesh_terms: D000818:Animals; D020746:Calcium Channels, L-Type / Q000235:genetics / Q000502:physiology; D058534:Class I Phosphatidylinositol 3-Kinases; D004285:Dogs; D005260:Female; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009200:Myocardial Contraction / Q000235:genetics*; D032383:Myocytes, Cardiac / Q000201:enzymology* / Q000473:pathology*; D019869:Phosphatidylinositol 3-Kinases / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
chemical_list: D020746:Calcium Channels, L-Type; D019869:Phosphatidylinositol 3-Kinases; C509622:1-phosphatidylinositol 3-kinase p110 subunit, mouse; D058534:Class I Phosphatidylinositol 3-Kinases