![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
2-Adrenergic Receptor Signaling in Ventricular Myocytes: the Role of Gi proteins and Caveolae Microdomains
Departments of Pharmacology (V.O.R., E.P., S.A., S.F.S.) and Medicine (S.F.S.), College of Physicians and Surgeons, Columbia University, New York, New York
Cardiomyocyte 
2-adrenergic receptors (-ARs) provide
a source of inotropic support and influence the evolution of heart failure.
Recent studies identify distinct mechanisms for 2-AR actions
in neonatal and adult rat cardiomyocytes. This study examines whether
ontogenic changes in cardiac 2-AR actions can be attributed
to altered Gi expression or changes in the spatial organization of the
2-AR complex in membrane subdomains (caveolae). We show that
2-ARs increase cAMP, calcium, and contractile amplitude in a
pertussis toxin (PTX)-insensitive manner in neonatal cardiomyocytes. This is
not caused by lack of Gi; G
i expression is higher in neonatal
cardiomyocytes than in those of adult rats. 2-ARs provide
inotropic support without detectably increasing cAMP, in adult cardiomyocytes.
This cannot be attributed to dual coupling of 2-ARs to Gs and
Gi, because 2-ARs do not promote cAMP accumulation in
PTX-pretreated adult cardiomyocytes. Spatial segregation of
2-ARs, Gs/Gi, and adenylyl cyclase to distinct
membrane subdomains also is not a factor, because all of these proteins
copurify in caveolin-3-enriched vesicles isolated from adult cardiomyocytes.
However, these studies demonstrate that enzyme-based protocols routinely used
to isolate ventricular cardiomyocytes lead to proteolysis of -ARs. The
functional consequences of this limited -AR proteolysis is uncertain,
because truncated 1-ARs promote cAMP accumulation and
truncated 2-ARs provide inotropic support in adult
cardiomyocytes. Collectively, these studies indicate that components of the
2-AR signaling complex compartmentalize to restricted
membrane subdomains in adult rat cardiomyocytes. Neither compartmentalization
nor changes in Gi expression fully explain the ontogenic changes in
2-AR responsiveness in the rat ventricle.
Address correspondence to: Dr. Susan F. Steinberg, Department of Pharmacology, College of Physicians and Surgeons, Columbia University, 630 West 168th Street, New York, NY 10032. E-mail: sfs1{at}columbia.edu
This article has been cited by other articles:
|
|
 |
|
  L. P. Collis, S. Srivastava, W. A. Coetzee, and M. Artman beta2-Adrenergic receptor agonists stimulate L-type calcium current independent of PKA in newborn rabbit ventricular myocytes Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H2826 - H2835. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Bauer, R. Becker, J. Dreyhaupt, F. Voss, P. Kraft, K. Kelemen, J. C. Senges-Becker, H. A. Katus, and W. Schoels Role of KATP channels in repetitive induction of ventricular fibrillation Europace, March 1, 2007; 9(3): 154 - 161. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Boivin, C. Lavoie, G. Vaniotis, A. Baragli, L.-R. Villeneuve, N. Ethier, P. Trieu, B. G. Allen, and T. E. Hebert Functional {beta}-adrenergic receptor signalling on nuclear membranes in adult rat and mouse ventricular cardiomyocytes Cardiovasc Res, July 1, 2006; 71(1): 69 - 78. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. C. Balijepalli, J. D. Foell, D. D. Hall, J. W. Hell, and T. J. Kamp From the Cover: Localization of cardiac L-type Ca2+ channels to a caveolar macromolecular signaling complex is required for beta2-adrenergic regulation PNAS, May 9, 2006; 103(19): 7500 - 7505. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Rochais, A. Abi-Gerges, K. Horner, F. Lefebvre, D. M.F. Cooper, M. Conti, R. Fischmeister, and G. Vandecasteele A Specific Pattern of Phosphodiesterases Controls the cAMP Signals Generated by Different Gs-Coupled Receptors in Adult Rat Ventricular Myocytes Circ. Res., April 28, 2006; 98(8): 1081 - 1088. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Calaghan and E. White Caveolae modulate excitation-contraction coupling and {beta}2-adrenergic signalling in adult rat ventricular myocytes Cardiovasc Res, March 1, 2006; 69(4): 816 - 824. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Germack and J. M. Dickenson Induction of {beta}3-Adrenergic Receptor Functional Expression following Chronic Stimulation with Noradrenaline in Neonatal Rat Cardiomyocytes J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 392 - 402. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. P. Head, H. H. Patel, D. M. Roth, N. C. Lai, I. R. Niesman, M. G. Farquhar, and P. A. Insel G-protein-coupled Receptor Signaling Components Localize in Both Sarcolemmal and Intracellular Caveolin-3-associated Microdomains in Adult Cardiac Myocytes J. Biol. Chem., September 2, 2005; 280(35): 31036 - 31044. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Rudajev, J. Novotny, L. Hejnova, G. Milligan, and P. Svoboda Dominant Portion of Thyrotropin-Releasing Hormone Receptor Is Excluded from Lipid Domains. Detergent-Resistant and Detergent-Sensitive Pools of TRH Receptor and Gq{alpha}/G11{alpha} Protein J. Biochem., August 1, 2005; 138(2): 111 - 125. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-G. Kerfant, D. Gidrewicz, H. Sun, G. Y. Oudit, J. M. Penninger, and P. H. Backx Cardiac Sarcoplasmic Reticulum Calcium Release and Load Are Enhanced by Subcellular cAMP Elevations in PI3K{gamma}-Deficient Mice Circ. Res., May 27, 2005; 96(10): 1079 - 1086. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Ait-Mamar, M. Cailleret, C. Rucker-Martin, A. Bouabdallah, G. Candiani, C. Adamy, P. Duvaldestin, F. Pecker, N. Defer, and C. Pavoine The Cytosolic Phospholipase A2 Pathway, a Safeguard of {beta}2-Adrenergic Cardiac Effects in Rat J. Biol. Chem., May 13, 2005; 280(19): 18881 - 18890. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. F. Steinberg The Cardiovascular Actions of Protease-Activated Receptors Mol. Pharmacol., January 1, 2005; 67(1): 2 - 11. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Iwatsubo, S. Minamisawa, T. Tsunematsu, M. Nakagome, Y. Toya, J. E. Tomlinson, S. Umemura, R. M. Scarborough, D. E. Levy, and Y. Ishikawa Direct Inhibition of Type 5 Adenylyl Cyclase Prevents Myocardial Apoptosis without Functional Deterioration J. Biol. Chem., September 24, 2004; 279(39): 40938 - 40945. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Barki-Harrington, C. Perrino, and H. A Rockman Network integration of the adrenergic system in cardiac hypertrophy Cardiovasc Res, August 15, 2004; 63(3): 391 - 402. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-P. Gratton, P. Bernatchez, and W. C. Sessa Caveolae and Caveolins in the Cardiovascular System Circ. Res., June 11, 2004; 94(11): 1408 - 1417. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Odley, H. S. Hahn, R. A. Lynch, Y. Marreez, H. Osinska, J. Robbins, and G. W. Dorn II Regulation of cardiac contractility by Rab4-modulated {beta}2-adrenergic receptor recycling PNAS, May 4, 2004; 101(18): 7082 - 7087. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
