on July 13, 2009
Published online before print July 13, 2009, doi: 10.1161/CIRCULATIONAHA.109.873380
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Submitted on August 14, 2009
From the Department of Physiology and Biophysics and Institute of Molecular Cardiology (Z.L., W.W., R.T.M., E.E., I.S.C., R.Z.L.) and Department of Medicine (Y.P.J., L.M.B., R.Z.L.), Stony Brook University, Stony Brook, NY; Department of Cardiac Surgery, Central South University, Changsha, China (X.H.X.); and Department of Veterans Affairs Medical Center, Northport, NY (R.Z.L.). * To whom correspondence should be addressed. E-mail: richard.lin{at}sunysb.edu.
Background—Phosphoinositide 3-kinase (PI3K) p110 Methods and Results—Genetic ablation of p110 Conclusions—PI3K p110
Accepted on May 5, 2009
Loss of Cardiac Phosphoinositide 3-Kinase p110
Zhongju Lu PhD, 
Results in Contractile Dysfunction
plays a key role in insulin action and tumorigenesis. Myocyte contraction is initiated by an inward Ca2+ current (ICa,L) through the voltage-dependent L-type Ca2+ channel (LTCC). The aim of this study was to evaluate whether p110 also controls cardiac contractility by regulating the LTCC. (also known as Pik3ca), but not p110
(also known as Pik3cb), in cardiac myocytes of adult mice reduced ICa,L and blocked insulin signaling in the heart. p110-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 p110 decreased ICa,L and contractility in canine myocytes. Inhibition of p110 did not reduce ICa,L. but not p110 regulates the LTCC in cardiac myocytes. Decreased signaling to p110 reduces the number of LTCCs on the cell surface and thus attenuates ICa,L and contractility.
Key words: calcium • ion channels • signal transduction • myocytes • contractility
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