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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