کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3031966 1183954 2006 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Phosphoinositide 3-kinase γ Regulates Cardiac Contractility by Locally Controlling Cyclic Adenosine Monophosphate Levels
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Phosphoinositide 3-kinase γ Regulates Cardiac Contractility by Locally Controlling Cyclic Adenosine Monophosphate Levels
چکیده انگلیسی

Class I phosphoinositide 3-kinases (PI3Ks) are enzymes with both protein and lipid kinase activities that regulate important cellular functions in many tissues. In the heart, subclass IA PI3Ks (mainly PI3Kα) regulate cell growth, apoptosis, cell division and cell size, whereas PI3Kγ, the only member of subclass IB, has been shown to regulate cardiac contractility. We have shown that the loss of PI3Kγ  (PI3Kγ−/− mice) enhances cardiac excitation–contraction coupling by modulating cyclic adenosine monophosphate (cAMP) levels in subcellular domains containing the sarcoplasmic reticulum. Specifically, PI3Kγ−/− mice show enhanced sarcoplasmic reticulum Ca2+ cycling in association with increased cAMP. Surprisingly, L-type Ca2+ current, a prototypic target of cAMP-dependent protein kinase A phosphorylation, is largely unchanged in PI3Kγ−/− mice. In this article, we discuss the consequences and implications of cAMP compartmentation in cardiomyocytes. We also review the different roles of PI3Kγ in the heart, particularly as they relate to cardiac contractility, intracellular cAMP levels, and the regulation of β-adrenergic receptor signaling in physiologic and pathologic states.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Trends in Cardiovascular Medicine - Volume 16, Issue 7, October 2006, Pages 250–256
نویسندگان
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