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Signal Transduction and Cardiac Hypertrophy pp 323–334Cite as

Compartmentation to Lipid Rafts as a Mechanism to Regulate β-adrenergic Receptor Signaling in Cardiomyocytes

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Part of the book series: Progress in Experimental Cardiology ((PREC,volume 7))

Summary

The traditional notion that cardiomyocyte β1- and β2-adrenergic receptors signal in an identical fashion to adenylyl cyclase and the accumulation of cAMP has been challenged by recent studies demonstrating that: (1)β1- and β2-adrenergic receptors promote a marked increase in cAMP accumulation and exert positive inotropic/lusitropic responses in neonatal rat cardiomyocytes; β1-adrenergic receptors increase cAMP in adult rat cardiomyocytes, but β2-adrenergic receptors increase twitch amplitude, without inducing a detectable elevation of intracellular cAMP or accelerating the kinetics of relaxation, in adult rat cardiomyocytes. (2) In neonatal rat cardiomyocytes (where both β1- and β2-adrenergic receptors increase cAMP accumulation), the β1-adrenergic receptor pathway is highly sensitive to inhibitory modulation by muscarinic cholinergic agonists, whereas the β2-adrenergic receptor-dependent increase in cAMP accumulation is not. (33) Overexpression of type VI adenylyl cyclase in neonatal rat cardiomyocytes leads to a selective increase in β-adrenergic receptor-dependent signaling to cAMP formation, without changing cAMP accumulation by agonists of prostenoid, adenosine, glucagon, or histamine receptors. This type of specificity for β-adrenergic receptor subtype signaling cannot be explained by traditional concepts that focus on high-affinity protein-protein interactions between receptors, G proteins, and effectors (freely mobile in the plasma membrane) as the prime determinants of signaling specificity. This chapter summarizes recent studies that identify spatial localization to membrane subdomains (caveolae/lipid rafts) as a mechanism to calibrate β-adrenergic receptor signaling in cardiomyocytes. This mechanism might be pertinent to the pathogenesis of heart failure, where β-adrenergic receptor signaling is augmented.

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References

  1. Cohn JN, Levine TB, Olivari MT, Garberg V, Lura D, Francis GS, Simon AB, Rector T. 1984. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 311:819–823.

    Article  PubMed  CAS  Google Scholar 

  2. Packer M. 1998. Beta-blockade in heart failure. Basic concepts and clinical results. Am J Hypertens 11:23S–37S.

    Article  PubMed  CAS  Google Scholar 

  3. Liggett SB,Tepe NM, Lorenz JN, Canning AM, Jantz TD, Mitarai S,Yatani A, Dorn GW. 2000. Early and delayed consequences of β2-adrenergic receptor overexpression in mouse hearts: critical role for expression level. Circulation 101:1707–1714.

    Article  PubMed  CAS  Google Scholar 

  4. Engelhardt S, Hein L, Wiesmann F, Lohse MJ. 1999. Progressive hypertrophy and heart failure in β1-adrenergic receptor transgenic mice. Proc Natl Acad Sei U S A 96:7059–7064.

    Article  CAS  Google Scholar 

  5. Bisognano JD, Weinberger HD, Bohlmeyer TJ, Pende A, Raynolds MV, Sastravaha A, Roden R, Asano K, Blaxall BC, Wu SC, Communal C, Singh K, Colucci W, Bristow MR, Port DJ. 2000. Myocardial-directed overexpression of the human β1-adrenergic receptor in transgenic mice. J Mol Cell Cardiol 32:817–830.

    Article  PubMed  CAS  Google Scholar 

  6. Chesley A, Lundberg MS, Asai T, Xiao RP, Ohtani S, Lakatta EG, Crow MT. 2000. The β2-adrenergic receptor delivers an anti-apoptotic signal to cardiac myocyte through Gi-dependent coupling to phosphatidylinositol 3′-kinase. Circ Res 87:1172–1179.

    Article  PubMed  CAS  Google Scholar 

  7. Kaumann AJ, Sanders L, Lynham J, Bartel S, Kuschel M, Karczewski P, Krause EG. 1996. β2-adrenoceptor activation by zinterol causes protein phosphorylation, contractile effects and relaxant effects through a cAMP pathway in human atrium. Mol Cell Biochem 163/164:113–123.

    Article  Google Scholar 

  8. Kaumann A, Bartel S, Molenaar P, Sanders L, Burrell K, Vetter D, Hempel P, Karczewski P, Krause EG. 1999. Activation of β2-adrenergic receptors hastens relaxation and mediates phosphorylation of phospholamban, troponin I. and C-protein in ventricular myocardium from patients with terminal heart failure. Circulation 99:65–72.

    Article  PubMed  CAS  Google Scholar 

  9. Stamatelopoulou SI, Mittmann C, Eschenhagen T. 1999. β-Adrenergic stimulation of azidoanilido [32P]-GTP binding to Gs and Gi/Go proteins in human myocardial membranes. Circulation 100:I-487.

    Google Scholar 

  10. Steinberg SF 2000. The cellular actions of β-adrenergic receptor agonists: Looking beyond cAMP. Circ Res 87:1079–1082.

    Article  PubMed  CAS  Google Scholar 

  11. Kuznetsov V, Pak E, Robinson RB, Steinberg SF. 1995. β2-Adrenergic receptor actions in neonatal and adult rat ventricular myocytes. Circ Res 76:40–52.

    Article  PubMed  Google Scholar 

  12. Steinberg SF. 1999. The molecular basis for distinct β-adrenergic receptor subtype actions in car-diomyocytes. Circ Res 85:1101–1111.

    Article  PubMed  CAS  Google Scholar 

  13. Laflamme MA, Becker PL. 1998. Do β2-adrenergic receptors modulate Ca2+ in adult rat ventricular myocytes? Am J Physiol 274:H1308-H1314.

    PubMed  CAS  Google Scholar 

  14. Sabri A, Pak E, Alcott SA, Wilson BA, Steinberg SF. 2000. Coupling function of endogenous α1-and β-adrenergic receptors in mouse cardiomyocytes. Circ Res 86:1047–1053.

    Article  PubMed  CAS  Google Scholar 

  15. Altschuld RA, Starling RC, Hamlin RL, Billman GE, Hensley J, Castillo L, Fertel RH, Hohl CM, Robitaille PML, Jones LR, Xiao RP, Lakatta EG. 1995. Response of failing canine and human heart cells to β2-adrenergic stimulation. Circulation 92:1612–1618.

    Article  PubMed  CAS  Google Scholar 

  16. Ostrom RS, Gregorian C, Drenan RM, Xiang Y, Regan JW, Insel PA. 2001. Receptor number and caveolar co-localization determine receptor coupling efficiency to adenylyl cyclase. J Biol Chem 276:42063–42069.

    Article  PubMed  CAS  Google Scholar 

  17. Xiao RP, Cheng H, Zhou YY, Kuschel M, Lakatta EG. 1999. Recent advances in cardiac β2-adren-ergic signal transduction. Circ Res 85:1092–1100.

    Article  PubMed  CAS  Google Scholar 

  18. Jiang T, Steinberg SF. 1997. drenergic receptors enhance contractility by stimulating HCO3 --dependent intracellular alkalinization. Am J Physiol 273:H1044-H1047.

    PubMed  Google Scholar 

  19. Aprigliano O, Rybin VO, Pak E, Robinson RB, Steinberg SF. 1997. β1- and β2-adrenergic receptors exhibit differing susceptibility to muscarinic accentuated antagonism. Am J Physiol 272:H2726-H2735.

    PubMed  Google Scholar 

  20. Ostrom RS, Violin JD, Coleman S, Insel PA. 2000. Selective enhancement of beta-adrenergic receptor signaling by overexpression of adenylyl cyclase type 6: colocalization of receptor and adenylyl cyclase in caveolae of cardiac myocytes. Mol Pharmacol 57:1075–1079.

    PubMed  CAS  Google Scholar 

  21. Steinberg SF, Brunton LL. 2001. Compartmentalization of G-protein-mediated signal transduction components in the heart. Ann Rev Pharm Tox 41:751–773.

    Article  CAS  Google Scholar 

  22. Okamoto T, Schlegel A, Scherer PE, Lisanti MP. 1998. Caveolins, a family of scaffolding proteins for organizing “preassembled signaling complexes” at the plasma membrane. J Biol Chem 273: 5419–5422.

    Article  PubMed  CAS  Google Scholar 

  23. Razani B, Schlegel A, Lisanti MP. 2000. Caveolin proteins in signaling, oncogenic transformation and muscular dystrophy. J Cell Sci 113:2103–2109.

    PubMed  CAS  Google Scholar 

  24. Schwencke C, Okumura S, Yamamoto M, Geng YJ, Ishikawa Y. 1999. Colocalization of beta-adrenergic receptors and caveolin within the plasma membrane. J Cell Biochem 75:64–72.

    Article  PubMed  CAS  Google Scholar 

  25. Rybin VO, Xu X, Lisanti MP, Steinberg SF. 2000. Differential targeting of beta-adrenergic receptor subtypes and adenylyl cyclase to cardiomyocyte caveolae: A mechanism to functionally regulate the cAMP signaling pathway. J Biol Chem 275:41447–41457.

    Article  PubMed  CAS  Google Scholar 

  26. Green SA, Liggett SB. 1994. A proline-rich region of the third intracellular loop imparts pheno-typic β1-versus β2-adrenergic receptor coupling and sequestration. J Biol Chem 269:26215–26219.

    PubMed  CAS  Google Scholar 

  27. Hohl CM, Li Q. 1991. Compartmentation of cAMP in adult canine ventricular myocytes: Relation to single-cell free Ca2+ transients. Circ Res 69:1369–1379.

    Article  PubMed  CAS  Google Scholar 

  28. Fagan KA, Smith KE, Cooper DMF. 2000. Regulation of the Ca2+-inhibitable adenylyl cyclase type VI by capacitative Ca2+ entry requires localization in cholesterol-rich domains. J Biol Chem 275:26530–26537.

    Article  PubMed  CAS  Google Scholar 

  29. Schwencke C,Yamamoto M, Okumura S, Toya Y, Kim SJ, Ishikawa Y. 1999. Compartmentation of cyclic adenosine 3′,5′-monophosphate signaling in caveolae. Mol Endocrinol 13:1061–1070.

    Article  PubMed  CAS  Google Scholar 

  30. Toya Y, Schwencke C, Couet J, Lisanti MP, Ishikawa Y. 1998. Inhibition of adenylyl cyclase by caveolin peptides. Endocrinology 139:2025–2031.

    Article  PubMed  CAS  Google Scholar 

  31. Martens JR, Navarro-Polanco R, Coppock EA, Nishiyama A, Parshley L, Grobaski TD,Tamkun MM. 2000. Differential targeting of Shaker-like potassium channels to lipid rafts. J Biol Chem 275: 7443–7446.

    Article  PubMed  CAS  Google Scholar 

  32. Melkonian KA, Ostermeyer AG, Chen JZ, Roth MG, Brown DA. 1999. Role of lipid modifications in targeting proteins to detergent-resistant membrane rafts. Many raft proteins are acylated, while few are prenylated. J Biol Chem 274:3910–3917.

    Article  PubMed  CAS  Google Scholar 

  33. Minetti C, Sotgia F, Bruno C, Scartezzini P, Broda P, Bado M, Masetti E, Mazzocco M, Egeo A, Donati MA, Volonte D, Galbiati F, Cordone G, Bricarelli FD, Lisanti MP, Zara F. 1998. Mutations in the caveolin-3 gene cause autosomal dominant limb-girdle muscular dystrophy. Nature Genetics 18:365–368.

    Article  PubMed  CAS  Google Scholar 

  34. Galbiati F, Volonte D, Minetti C, Chu JB, Lisanti MP. 1999. Phenotypic behavior of caveolin-3 mutations that cause autosomal dominant limb girdle muscular dystrophy (LGMD-1C). Retention of LGMD-1C caveolin-3 mutants within the golgi complex. J Biol Chem 274:25632–25641.

    Article  PubMed  CAS  Google Scholar 

  35. Schlegel A, Lisanti MP. 2001. The caveolin triad: caveolae biogenesis, cholesterol trafficking, and signal transduction. Cytokine Growth Factor Rev 12:41–51.

    Article  PubMed  CAS  Google Scholar 

  36. Galbiati F, Engelman JA, Volonte D, Zhang XL, Minetti C, Li M, Hou H, Jr., Kneitz B, Edelmann W, Lisanti MP. 2001. Caveolin-3 null mice show a loss of caveolae, changes in the microdomain distribution of the dystrophin-glycoprotein complex, and T-tubule abnormalities. J Biol Chem 276:21425–21433.

    Article  PubMed  CAS  Google Scholar 

  37. Hagiwara Y, Sasaoka T, Araishi K, Imamura M, Yorifuji H, Nonaka I, Ozawa E, Kikuchi T. 2000. Caveolin-3 deficiency causes muscle degeneration in mice. Hum Mol Genet 9:3047–3054.

    Article  PubMed  CAS  Google Scholar 

  38. Yamamoto M, Okumura S, Oka N, Schwencke C, Ishikawa Y 1999. Downregulation of caveolin expression by cAMP signal. Life Sci 64:1349–1357.

    Article  PubMed  CAS  Google Scholar 

  39. Hare JM, Lofthouse RA, Juang GJ, Colman L, Ricker KM, Kim B, Senzaki H, Cao S, Tunin RS, Kass DA. 2000. Contribution of caveolin protein abundance to augmented nitric oxide signaling in conscious dogs with pacing-induced heart failure. Circ Res 86:1085–1092.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Departments of Pharmacology, College of Physicians and Surgeons, Columbia University, 630 West 168 Street, New York, New York, 10032, USA

    Susan F. Steinberg M.D. (Associate Professor of Pharmacology and Medicine)

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  1. Susan F. Steinberg M.D.
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Correspondence to Susan F. Steinberg M.D. .

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Editors and Affiliations

  1. Institute of Cardiovascular Sciences, St. Boniface General Hospital Research Centre Faculty of Medicine, University of Manitoba, Winnipeg, Canada

    Naranjan S. Dhalla PhD, MD (Hon), DSc (Hon) (Distinguished Professor and Director), Larry V. Hryshko PhD (Associate Professor), Elissavet Kardami PhD (Professor) & Pawan K. Singal PhD, DSc (Professor) (Distinguished Professor and Director),  (Associate Professor),  (Professor) &  (Professor)

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Steinberg, S.F. (2003). Compartmentation to Lipid Rafts as a Mechanism to Regulate β-adrenergic Receptor Signaling in Cardiomyocytes. In: Dhalla, N.S., Hryshko, L.V., Kardami, E., Singal, P.K. (eds) Signal Transduction and Cardiac Hypertrophy. Progress in Experimental Cardiology, vol 7. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0347-7_23

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  • DOI: https://doi.org/10.1007/978-1-4615-0347-7_23

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5032-3

  • Online ISBN: 978-1-4615-0347-7

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