Trends in Cardiovascular Medicine
Volume 16, Issue 7 , Pages 250-256 , October 2006

Phosphoinositide 3-kinase γ Regulates Cardiac Contractility by Locally Controlling Cyclic Adenosine Monophosphate Levels

  • Benoit-Gilles Kerfant

      Affiliations

    • Both authors contributed equally to this work.
    • ,
  • Robert A. Rose

      Affiliations

    • Both authors contributed equally to this work.
    • ,
  • Hui Sun
    • ,
  • Peter H. Backx

      Affiliations

    • Corresponding Author InformationAddress correspondence to: Peter H. Backx, DVM, PhD, Fitzgerald Building, Heart and Stroke/Richard Lewar Center- 150 College St., Toronto, Ontario, Canada M5S 3E2. Tel.: (+1) 416-946-8112; fax: (+1) 416-340-8380.

References 

  1. Alloatti G, Marcantoni A, Levi R, et al. Phosphoinositide 3-kinase gamma controls autonomic regulation of the mouse heart through Gi-independent downregulation of cAMP level. FEBS Lett. 2005;579:133–140
  2. Baillie GS, Sood A, McPhee I, et al. beta-Arrestin-mediated PDE4 cAMP phosphodiesterase recruitment regulates beta-adrenoceptor switching from Gs to Gi. Proc Natl Acad Sci U S A. 2003;100:940–945
  3. Baillie GS, Scott JD, Houslay MD. Compartmentalisation of phosphodiesterases and protein kinase A: opposites attract. FEBS Lett. 2005;579:3264–3270
  4. Bauman AL, Scott JD. Kinase- and phosphatase-anchoring proteins: harnessing the dynamic duo. Nat Cell Biol. 2002;4:E203–E206
  5. Beavo JA. Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms. Physiol Rev. 1995;75:725–748
  6. Benitah JP, Gomez AM, Fauconnier J, et al. Voltage-gated Ca2+ currents in the human pathophysiologic heart: a review. Basic Res Cardiol. 2002;97(Suppl 1):1/11–1/18
  7. Bers DM. Cardiac excitation–contraction coupling. Nature. 2002;415:198–205
  8. Bers DM, Ziolo MT. When is cAMP not cAMP? Effects of compartmentalization. Circ Res. 2001;89:373–375
  9. Bers DM, Eisner DA, Valdivia HH. Sarcoplasmic reticulum Ca2+ and heart failure: roles of diastolic leak and Ca2+ transport. Circ Res. 2003;93:487–490
  10. Beuckelmann DJ, Nabauer M, Erdmann E. Intracellular calcium handling in isolated ventricular myocytes from patients with terminal heart failure. Circulation. 1992;85:1046–1055
  11. Bohm M, Flesch M, Schnabel P. Beta-adrenergic signal transduction in the failing and hypertrophied myocardium. J Mol Med. 1997;75:842–848
  12. Camps M, Ruckle T, Ji H, et al. Blockade of PI3Kgamma suppresses joint inflammation and damage in mouse models of rheumatoid arthritis. Nat Med. 2005;11:936–943
  13. Chen-Izu Y, Xiao RP, Izu LT, et al. G(i)-dependent localization of beta(2)-adrenergic receptor signaling to L-type Ca(2+) channels. Biophys J. 2000;79:2547–2556
  14. Chesley A, Lundberg MS, Asai T, et al. The beta(2)-adrenergic receptor delivers an antiapoptotic signal to cardiac myocytes through G(i)-dependent coupling to phosphatidylinositol 3'-kinase. Circ Res. 2000;87:1172–1179
  15. Crackower MA, Oudit GY, Kozieradzki I, et al. Regulation of myocardial contractility and cell size by distinct PI3K–PTEN signaling pathways. Cell. 2002;110:737–749
  16. Dedkova EN, Wang YG, Blatter LA, et al. Nitric oxide signalling by selective beta(2)-adrenoceptor stimulation prevents ACh-induced inhibition of beta(2)-stimulated Ca(2+) current in cat atrial myocytes. J Physiol. 2002;542(Pt. 3):711–723
  17. Georget M, Mateo P, Vandecasteele G, et al. Cyclic AMP compartmentation due to increased cAMP-phosphodiesterase activity in transgenic mice with a cardiac-directed expression of the human adenylyl cyclase type 8 (AC8). FASEB J. 2003;17:1380–1391
  18. Gomez AM, Valdivia HH, Cheng H, et al. Defective excitation–contraction coupling in experimental cardiac hypertrophy and heart failure. Science. 1997;276:800–806
  19. Gwathmey JK, Copelas L, MacKinnon R, et al. Abnormal intracellular calcium handling in myocardium from patients with end-stage heart failure. Circ Res. 1987;61:70–76
  20. Hirsch E, Katanaev VL, Garlanda C, et al. Central role for G protein-coupled phosphoinositide 3-kinase gamma in inflammation. Science. 2000;287(5455):1049–1053
  21. Jo SH, Leblais V, Wang PH, et al. Phosphatidylinositol 3-kinase functionally compartmentalizes the concurrent G(s) signaling during beta2-adrenergic stimulation. Circ Res. 2002;91(1):46–53
  22. Jurevicius J, Fischmeister R. cAMP compartmentation is responsible for a local activation of cardiac Ca2+ channels by beta-adrenergic agonists. Proc Natl Acad Sci U S A. 1996;93(1):295–299
  23. Keely SL. Prostaglandin E1 activation of heart cAMP-dependent protein kinase: apparent dissociation of protein kinase activation from increases in phosphorylase activity and contractile force. Mol Pharmacol. 1979;15(2):235–245
  24. Kerfant BG, Oudit GY, Backx PH. Pi3Kgamma alters Gi activity while maintaining ICa-L and IKAch densities. 48th Annual Meeting of the Biophysical Society. Biophys J. 2004;86(1, Pt2.):296a
  25. Kerfant BG, Gidrewicz D, Sun H, et al. Cardiac sarcoplasmic reticulum calcium release and load are enhanced by subcellular cAMP elevations in PI3Kgamma-deficient mice. Circ Res. 2005;96(10):1079–1086
  26. Kuschel M, Zhou YY, Cheng H, et al. G(i) protein-mediated functional compartmentalization of cardiac beta(2)-adrenergic signaling. J Biol Chem. 1999;274(31):22048–22052
  27. Leblais V, Jo SH, Chakir K, et al. Phosphatidylinositol 3-kinase offsets cAMP-mediated positive inotropic effect via inhibiting Ca2+ influx in cardiomyocytes. Circ Res. 2004;95(12):1183–1190
  28. Lehnart SE, Wehrens XH, Reiken S, et al. Phosphodiesterase 4D deficiency in the ryanodine-receptor complex promotes heart failure and arrhythmias. Cell. 2005;123(1):25–35
  29. Luo J, McMullen JR, Sobkiw CL, et al. Class IA phosphoinositide 3-kinase regulates heart size and physiological cardiac hypertrophy. Mol Cell Biol. 2005;25(21):9491–9502
  30. Marcantoni A, Levi R, Gallo MP, et al. Phosphoinositide 3 kinaseγ (PI3Kγ) controls L-type calcium current (ICa,L) through its positive modulation of type-phosphodiestrase (PDE3). J Cell Physiol. 2006;206(2):329–336
  31. Maurice DH, Palmer D, Tilley DG, et al. Cyclic nucleotide phosphodiesterase activity, expression, and targeting in cells of the cardiovascular system. Mol Pharmacol. 2003;64(3):533–546
  32. Mongillo M, McSorley T, Evellin S, et al. Fluorescence resonance energy transfer-based analysis of cAMP dynamics in live neonatal rat cardiac myocytes reveals distinct functions of compartmentalized phosphodiesterases. Circ Res. 2004;95(1):67–75
  33. Movsesian MA. PDE3 cyclic nucleotide phosphodiesterases and the compartmentation of cyclic nucleotide-mediated signalling in cardiac myocytes. Basic Res Cardiol. 2002;97(Suppl 1):I83–I90
  34. Naga Prasad SV, Esposito G, Mao L, et al. Gbetagamma-dependent phosphoinositide 3-kinase activation in hearts with in vivo pressure overload hypertrophy. J Biol Chem. 2000;275(7):4693–4698
  35. Naga Prasad SV, Barak LS, Rapacciuolo A, et al. Agonist-dependent recruitment of phosphoinositide 3-kinase to the membrane by beta-adrenergic receptor kinase 1. A role in receptor sequestration. J Biol Chem. 2001;276(22):18953–18959
  36. Naga Prasad SV, Jayatilleke A, Madamanchi A, et al. Protein kinase activity of phosphoinositide 3-kinase regulates beta-adrenergic receptor endocytosis. Nat Cell Biol. 2005;7(8):785–796
  37. Netticadan T, Temsah RM, Kawabata K, et al. Sarcoplasmic reticulum Ca(2+)/calmodulin-dependent protein kinase is altered in heart failure. Circ Res. 2000;86(5):596–605
  38. Nienaber JJ, Tachibana H, Naga Prasad SV, et al. Inhibition of receptor-localized PI3K preserves cardiac {beta}-adrenergic receptor function and ameliorates pressure overload heart failure. J Clin Invest. 2003;112(7):1067–1079
  39. Oudit GY, Crackower MA, Eriksson U, et al. Phosphoinositide 3-kinase gamma-deficient mice are protected from isoproterenol-induced heart failure. Circulation. 2003;108(17):2147–2152
  40. Oudit GY, Sun H, Kerfant BG, et al. The role of phosphoinositide-3 kinase and PTEN in cardiovascular physiology and disease. J Mol Cell Cardiol. 2004;37(2):449–471
  41. Patrucco E, Notte A, Barberis L, et al. PI3Kgamma modulates the cardiac response to chronic pressure overload by distinct kinase-dependent and -independent effects. Cell. 2004;118(3):375–387
  42. Pavoine C, Defer N. The cardiac beta2-adrenergic signalling a new role for the cPLA2. Cell Signal. 2005;17(2):141–152
  43. Prasad SV, Perrino C, Rockman HA. Role of phosphoinositide 3-kinase in cardiac function and heart failure. Trends Cardiovasc Med. 2003;13(5):206–212
  44. Sahu A, Metlakunta AS. Hypothalamic phosphatidylinositol 3-kinase-phosphodiesterase 3B-cyclic AMP pathway of leptin signalling is impaired following chronic central leptin infusion. J Neuroendocrinol. 2005;17(11):720–726
  45. Sasaki T, Irie-Sasaki J, Jones RG, et al. Function of PI3Kgamma in thymocyte development, T cell activation, and neutrophil migration. Science. 2000;287(5455):1040–1046
  46. Steinberg SF, Brunton LL. Compartmentation of G protein-coupled signaling pathways in cardiac myocytes. Annu Rev Pharmacol Toxicol. 2001;41:751–773
  47. Sun H, Kerfant BG, Zhao D, et al. Insulin-like growth factor-1 and PTEN deletion enhance cardiac L-type Ca2+ currents via increased PI3Kα/PKB signaling. Circ Res. 2006;
  48. Takahashi K, Osanai T, Nakano T, et al. Enhanced activities and gene expression of phosphodiesterase types 3 and 4 in pressure-induced congestive heart failure. Heart Vessels. 2002;16(6):249–256
  49. Verde I, Vandecasteele G, Lezoualc'h F, et al. Characterization of the cyclic nucleotide phosphodiesterase subtypes involved in the regulation of the L-type Ca2+ current in rat ventricular myocytes. Br J Pharmacol. 1999;127(1):65–74
  50. Vila Petroff MG, Egan JM, Wang X, et al. Glucagon-like peptide-1 increases cAMP but fails to augment contraction in adult rat cardiac myocytes. Circ Res. 2001;89(5):445–452
  51. Voigt P, Dorner MB, Schaefer M. Characterization of p87PiKAP, a novel regulatory subunit of phosphoinositide 3-kinase gamma that is highly expressed in heart and interacts with PDE3B. J Biol Chem. 2006;281:9977–9986
  52. Wang YG, Dedkova EN, Steinberg SF, et al. Beta 2-adrenergic receptor signaling acts via NO release to mediate ACh-induced activation of ATP-sensitive K+ current in cat atrial myocytes. J Gen Physiol. 2002;119(1):69–82
  53. Wong W, Scott JD. AKAP signalling complexes: focal points in space and time. Nat Rev Mol Cell Biol. 2004;5(12):959–970
  54. Zhou YY, Song LS, Lakatta EG, et al. Constitutive beta2-adrenergic signalling enhances sarcoplasmic reticulum Ca2+ cycling to augment contraction in mouse heart. J Physiol. 1999;521(Pt. 2):351–361
  55. Zhu WZ, Zheng M, Koch WJ, et al. Dual modulation of cell survival and cell death by beta(2)-adrenergic signaling in adult mouse cardiac myocytes. Proc Natl Acad Sci U S A. 2001;98(4):1607–1612

PII: S1050-1738(06)00073-9

doi: 10.1016/j.tcm.2006.04.006

Trends in Cardiovascular Medicine
Volume 16, Issue 7 , Pages 250-256 , October 2006

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