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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 RIS Download

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

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Associated grants

  • Agency: NHLBI NIH HHS, Id: T32 HL07312
  • Agency: NHLBI NIH HHS, Id: T32 HL007312
  • Agency: NIGMS NIH HHS, Id: R01 GM032875
  • Agency: Howard Hughes Medical Institute, Id: R01 HL085372
  • Agency: NHLBI NIH HHS, Id: R01 HL088366
  • Agency: NHLBI NIH HHS, Id: R01 GM32875
  • Agency: NIGMS NIH HHS, Id:

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