| Protein kinase inhibitors reduce SR Ca transport in permeabilized cardiac myocytes. | |
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MedLine Citation:
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PMID: 8067437 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Phosphorylation of the sarcoplasmic reticulum (SR) protein phospholamban by adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase (PKA) and Ca-calmodulin-dependent protein kinase (CaM-KII) stimulates Ca-adenosinetriphosphatase (ATPase) activity and SR Ca transport, but the role of CaM-KII-dependent phosphorylation is not well defined. We studied the PKA- and CaM-KII-dependent regulation of SR Ca transport in digitonin-permeabilized rabbit ventricular myocytes. SR Ca uptake and free Ca concentration were measured on line with indo 1 and Ca electrodes in the presence of 20 microM ruthenium red and 10 mM oxalate. neither N5,2'-w-dibutyryl-cAMP (up to 500 microM) nor the nonhydrolyzable cAMP agonist adenosine 3'5'-cyclic monophosphorothioate sodium salt (Sp-cAMP[S]; up to 275 microM) affected the maximum uptake rate (Vmax) or the dissociation constant (Kd) for Ca uptake. However, the PKA inhibitor H-89 significantly increased Kd (e.g., from 307 +/- 67 to 826 +/- 62 nM Ca at 40-65 microM H-89) without significantly affecting Vmax. Both CaM-KII inhibitors, KN-62 (60 microM) and a CaM-KII inhibitory peptide (10 microM), significantly decreased Vmax from 11.95 +/- 0.5 to 9.48 +/- 0.6 nmol.mg-1.min-1 and from 10.95 +/- 1.72 to 7.37 +/- 0.94 nmol.mg-1.min-1, respectively, without consistently changing Kd. The effects of H-89 on Kd and of KN-62 on Vmax were prevented by a monoclonal antibody to phospholamban 2D12 (consistent with the antibody removing the inhibitory effect of phospholamban on the SR Ca-ATPase).(ABSTRACT TRUNCATED AT 250 WORDS) |
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Authors:
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A Mattiazzi; L Hove-Madsen; D M Bers |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The American journal of physiology Volume: 267 ISSN: 0002-9513 ISO Abbreviation: Am. J. Physiol. Publication Date: 1994 Aug |
Date Detail:
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Created Date: 1994-09-21 Completed Date: 1994-09-21 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0370511 Medline TA: Am J Physiol Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: H812-20 Citation Subset: IM |
Affiliation:
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Department of Physiology, Loyola University Medical School, Maywood, Illinois 60153. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine*
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analogs & derivatives* Animals Antibodies, Monoclonal / immunology Biological Transport Calcium / metabolism* Calcium-Binding Proteins / immunology Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors Cell Membrane Permeability Cyclic AMP-Dependent Protein Kinases / metabolism Enzyme Activation Isoquinolines / antagonists & inhibitors Myocardium / cytology, metabolism* Piperazines / antagonists & inhibitors Protein Kinase Inhibitors* Rabbits Sarcoplasmic Reticulum / metabolism* Sulfonamides* |
| Grant Support | |
ID/Acronym/Agency:
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HL-30077/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Calcium-Binding Proteins; 0/Isoquinolines; 0/Piperazines; 0/Protein Kinase Inhibitors; 0/Sulfonamides; 0/phospholamban; 127191-97-3/KN 62; 127243-85-0/H 89; 7440-70-2/Calcium; 84477-87-2/1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; EC 2.7.11.11/Cyclic AMP-Dependent Protein Kinases; EC 2.7.11.17/Calcium-Calmodulin-Dependent Protein Kinases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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