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Control of myocardial contractile function by the level of beta-adrenergic receptor kinase 1 in gene-targeted mice.

Publication ,  Journal Article
Rockman, HA; Choi, DJ; Akhter, SA; Jaber, M; Giros, B; Lefkowitz, RJ; Caron, MG; Koch, WJ
Published in: J Biol Chem
July 17, 1998

We studied the effect of alterations in the level of myocardial beta-adrenergic receptor kinase betaARK1) in two types of genetically altered mice. The first group is heterozygous for betaARK1 gene ablation, betaARK1(+/-), and the second is not only heterozygous for betaARK1 gene ablation but is also transgenic for cardiac-specific overexpression of a betaARK1 COOH-terminal inhibitor peptide, betaARK1(+/-)betaARKct. In contrast to the embryonic lethal phenotype of the homozygous betaARK1 knockout (Jaber, M., Koch, W. J., Rockman, H. A., Smith, B., Bond, R. A., Sulik, K., Ross, J., Jr., Lefkowitz, R. J., Caron, M. G., and Giros, B. (1996) Proc. Natl. Acad. Sci. U. S. A. 93, 12974-12979), betaARK1(+/-) mice develop normally. Cardiac catheterization was performed in mice and showed a stepwise increase in contractile function in the betaARK1(+/-) and betaARK1(+/-)betaARKct mice with the greatest level observed in the betaARK1(+/-)betaARKct animals. Contractile parameters were measured in adult myocytes isolated from both groups of gene-targeted animals. A significantly greater increase in percent cell shortening and rate of cell shortening following isoproterenol stimulation was observed in the betaARK1(+/-) and betaARK1(+/-)betaARKct myocytes compared with wild-type cells, indicating a progressive increase in intrinsic contractility. These data demonstrate that contractile function can be modulated by the level of betaARK1 activity. This has important implications in disease states such as heart failure (in which betaARK1 activity is increased) and suggests that betaARK1 should be considered as a therapeutic target in this situation. Even partial inhibition of betaARK1 activity enhances beta-adrenergic receptor signaling leading to improved functional catecholamine responsiveness.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

July 17, 1998

Volume

273

Issue

29

Start / End Page

18180 / 18184

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Rhodopsin
  • Phosphorylation
  • Myocardium
  • Myocardial Contraction
  • Mice, Transgenic
  • Mice
  • Isoproterenol
  • In Vitro Techniques
  • Heart Rate
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Rockman, H. A., Choi, D. J., Akhter, S. A., Jaber, M., Giros, B., Lefkowitz, R. J., … Koch, W. J. (1998). Control of myocardial contractile function by the level of beta-adrenergic receptor kinase 1 in gene-targeted mice. J Biol Chem, 273(29), 18180–18184. https://doi.org/10.1074/jbc.273.29.18180
Rockman, H. A., D. J. Choi, S. A. Akhter, M. Jaber, B. Giros, R. J. Lefkowitz, M. G. Caron, and W. J. Koch. “Control of myocardial contractile function by the level of beta-adrenergic receptor kinase 1 in gene-targeted mice.J Biol Chem 273, no. 29 (July 17, 1998): 18180–84. https://doi.org/10.1074/jbc.273.29.18180.
Rockman HA, Choi DJ, Akhter SA, Jaber M, Giros B, Lefkowitz RJ, et al. Control of myocardial contractile function by the level of beta-adrenergic receptor kinase 1 in gene-targeted mice. J Biol Chem. 1998 Jul 17;273(29):18180–4.
Rockman, H. A., et al. “Control of myocardial contractile function by the level of beta-adrenergic receptor kinase 1 in gene-targeted mice.J Biol Chem, vol. 273, no. 29, July 1998, pp. 18180–84. Pubmed, doi:10.1074/jbc.273.29.18180.
Rockman HA, Choi DJ, Akhter SA, Jaber M, Giros B, Lefkowitz RJ, Caron MG, Koch WJ. Control of myocardial contractile function by the level of beta-adrenergic receptor kinase 1 in gene-targeted mice. J Biol Chem. 1998 Jul 17;273(29):18180–18184.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

July 17, 1998

Volume

273

Issue

29

Start / End Page

18180 / 18184

Location

United States

Related Subject Headings

  • beta-Adrenergic Receptor Kinases
  • Rhodopsin
  • Phosphorylation
  • Myocardium
  • Myocardial Contraction
  • Mice, Transgenic
  • Mice
  • Isoproterenol
  • In Vitro Techniques
  • Heart Rate