| BENEFICIAL EFFECTS OF SR33805 IN FAILING MYOCARDIUM. | |
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MedLine Citation:
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PMID: 21467075 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Aims: SR33805, a potent Ca(2+) channel blocker, increases cardiac myofilament Ca(2+) sensitivity in healthy rat cardiomyocytes. Therefore, the aim of the present study was to evaluate the effects of SR33805 on contractile properties in ischemic failing hearts after myocardial infarction (MI) in vivo and in vitro at the cellular level. Methods and Results: The effect of SR33805 (10 µM) was tested on the excitation-contraction coupling of cardiomyocytes isolated from rat with end-stage heart failure. Cell shortening and Ca(2+) transients were measured in intact cardiomyocytes, while contractile properties were determined in triton X100 permeabilized myocytes. Acute treatment with SR33805 restored the MI-altered cell shortening without affecting the Ca(2+) transient amplitude, suggesting an increase of myofilament Ca(2+) sensitivity in MI myocytes. Indeed, a SR33805-induced sensitization of myofilament activation was found, associated with a slight increase in myosin light chain-2 (MLC-2) phosphorylation and a more significant decrease on troponin I (TnI) phosphorylation. Decreased TnI phosphorylation was related to inhibition of protein kinase A activity by SR33805. Finally, administration of a single intraperitoneal bolus of SR33805 (20mg/kg) improved end systolic strain and fractional shortening of MI hearts. Conclusion: The present study indicates that treatment with SR33805 improved contractility of ischemic failing hearts after myocardial infarction in the rat by selectively modulating the phosphorylation status of sarcomeric regulatory proteins, which then sensitized the myofilaments to Ca(2+). Our results gave a proof of concept that manipulation of the Ca(2+) sensitivity of sarcomeric regulatory proteins can be used to improve contractility of a failing heart. |
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Authors:
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Younss Ait Mou; Attila Toth; Cécile Cassan; Daniel Czuriga; Pieter P Detombe; Zoltan Papp; Alain Lacampagne; Olivier Cazorla |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-4 |
Journal Detail:
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Title: Cardiovascular research Volume: - ISSN: 1755-3245 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-6 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0077427 Medline TA: Cardiovasc Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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INSERM U1046, Université Montpellier1, F-34295 Montpellier, France. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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