| Cardiomyocytes from AKAP7 knockout mice respond normally to adrenergic stimulation. | |
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MedLine Citation:
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PMID: 23035250 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2012-10-03 |
Journal Detail:
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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:
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Created Date: 2012-10-17 Completed Date: 2012-12-31 Revised Date: 2013-05-20 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 17099-104 Citation Subset: IM |
Affiliation:
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Department of Pharmacology, University of Washington, Seattle, WA 98195, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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A Kinase Anchor Proteins
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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:
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R01 GM32875/GM/NIGMS 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:
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0/A Kinase Anchor Proteins; 0/Adrenergic beta-Agonists; 0/Akap7 protein, mouse; 0/DNA Primers; 7440-70-2/Calcium; 7683-59-2/Isoproterenol; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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