• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

Cardiomyocytes from AKAP7 knockout mice respond normally to adrenergic stimulation.

Protein kinase A (PKA) is activated during sympathetic stimulation of the heart and phosphorylates key proteins involved in cardiac Ca(2+) handling, including the L-type Ca(2+) channel (Ca(V)1.2) and phospholamban (PLN). This results in acceleration and amplification of the beat-to-beat changes in cytosolic Ca(2+) in cardiomyocytes and, in turn, an increased rate and force of contraction. PKA is held in proximity to its substrates by protein scaffolds called A kinase anchoring proteins (AKAPs). It has been suggested that the short and long isoforms of AKAP7 (also called AKAP15/18) localize PKA in complexes with Ca(V)1.2 and PLN, respectively. We generated an AKAP7 KO mouse in which all isoforms were deleted and tested whether Ca(2+) current, intracellular Ca(2+) concentration, or Ca(2+) reuptake were impaired in isolated adult ventricular cardiomyocytes following stimulation with the β-adrenergic agonist isoproterenol. KO cardiomyocytes responded normally to adrenergic stimulation, as measured by whole-cell patch clamp or a fluorescent intracellular Ca(2+) indicator. Phosphorylation of Ca(V)1.2 and PLN were also unaffected by genetic deletion of AKAP7. Immunoblot and RT-PCR revealed that only the long isoforms of AKAP7 were detectable in ventricular cardiomyocytes. The results indicate that AKAP7 is not required for regulation of Ca(2+) handling in mouse cardiomyocytes.

Pubmed ID: 23035250

Authors

  • Jones BW
  • Brunet S
  • Gilbert ML
  • Nichols CB
  • Su T
  • Westenbroek RE
  • Scott JD
  • Catterall WA
  • McKnight GS

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

October 16, 2012

Associated Grants

  • Agency: NIGMS NIH HHS, Id: R01 GM32875
  • Agency: NHLBI NIH HHS, Id: R01 HL085372
  • Agency: NHLBI NIH HHS, Id: R01 HL085372
  • Agency: NHLBI NIH HHS, Id: R01 HL088366
  • Agency: NHLBI NIH HHS, Id: R01 HL088366
  • Agency: NHLBI NIH HHS, Id: T32 HL07312
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • A Kinase Anchor Proteins
  • Adrenergic beta-Agonists
  • Animals
  • Blotting, Southern
  • Calcium
  • Cyclic AMP-Dependent Protein Kinases
  • DNA Primers
  • Immunoblotting
  • Immunoprecipitation
  • Isoproterenol
  • Mice
  • Mice, Knockout
  • Myocardial Contraction
  • Myocytes, Cardiac
  • Patch-Clamp Techniques
  • Phosphorylation
  • Reverse Transcriptase Polymerase Chain Reaction