Document Detail


Cardiomyocytes from AKAP7 knockout mice respond normally to adrenergic stimulation.
MedLine Citation:
PMID:  23035250     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Brian W Jones; Sylvain Brunet; Merle L Gilbert; C Blake Nichols; Thomas Su; Ruth E Westenbroek; John D Scott; William A Catterall; G Stanley McKnight
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-10-03
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  109     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-17     Completed Date:  2012-12-31     Revised Date:  2013-12-04    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  17099-104     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
A Kinase Anchor Proteins / genetics,  metabolism*
Adrenergic beta-Agonists / pharmacology*
Animals
Blotting, Southern
Calcium / metabolism*
Cyclic AMP-Dependent Protein Kinases / metabolism*
DNA Primers / genetics
Immunoblotting
Immunoprecipitation
Isoproterenol / pharmacology*
Mice
Mice, Knockout
Myocardial Contraction / physiology*
Myocytes, Cardiac / drug effects*,  metabolism
Patch-Clamp Techniques
Phosphorylation
Reverse Transcriptase Polymerase Chain Reaction
Grant Support
ID/Acronym/Agency:
R01 GM32875/GM/NIGMS NIH HHS; R01 HL085372/HL/NHLBI NIH HHS; R01 HL085372/HL/NHLBI NIH HHS; R01 HL088366/HL/NHLBI NIH HHS; R01 HL088366/HL/NHLBI NIH HHS; T32 HL07312/HL/NHLBI NIH HHS; //Howard Hughes Medical Institute
Chemical
Reg. No./Substance:
0/A Kinase Anchor Proteins; 0/Adrenergic beta-Agonists; 0/Akap7 protein, mouse; 0/DNA Primers; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases; L628TT009W/Isoproterenol; SY7Q814VUP/Calcium
Comments/Corrections

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