| Phospholemman Deficiency in Postinfarct Hearts: Enhanced Contractility but Increased Mortality. | |
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MedLine Citation:
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PMID: 22686200 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Phospholemman (PLM) regulates [Na(+) ](i) , [Ca(2+) ](i) and contractility through its interactions with Na(+) -K(+) -ATPase (NKA) and Na(+) /Ca(2+) exchanger (NCX1) in the heart. Both expression and phosphorylation of PLM are altered after myocardial infarction (MI) and heart failure. We tested the hypothesis that absence of PLM regulation of NKA and NCX1 in PLM-knockout (KO) mice is detrimental. Three weeks after MI, wild-type (WT) and PLM-KO hearts were similarly hypertrophied. PLM expression was lower but fractional phosphorylation was higher in WT-MI compared to WT-sham hearts. Left ventricular ejection fraction was severely depressed in WT-MI but significantly less depressed in PLM-KO-MI hearts despite similar infarct sizes. Compared with WT-sham myocytes, the abnormal [Ca(2+) ], transient and contraction amplitudes observed in WT-MI myocytes were ameliorated by genetic absence of PLM. In addition, NCX1 current was depressed in WT-MI but not in PLM-KO-MI myocytes. Despite improved myocardial and myocyte performance, PLM-KO mice demonstrated reduced survival after MI. Our findings indicate that alterations in PLM expression and phosphorylation are important adaptations post-MI, and that complete absence of PLM regulation of NKA and NCX1 is detrimental in post-MI animals. Clin Trans Sci 2012; Volume #: 1-8. |
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Authors:
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M Ayoub Mirza; Susan Lane; Zequan Yang; Themis Karaoli; Kwame Akosah; John Hossack; Marcia McDuffie; Jufang Wang; Xue-Qian Zhang; Jianliang Song; Joseph Y Cheung; Amy L Tucker |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-3-27 |
Journal Detail:
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Title: Clinical and translational science Volume: 5 ISSN: 1752-8062 ISO Abbreviation: - Publication Date: 2012 Jun |
Date Detail:
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Created Date: 2012-6-12 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101474067 Medline TA: Clin Transl Sci Country: - |
Other Details:
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Languages: ENG Pagination: 235-242 Citation Subset: - |
Copyright Information:
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© 2012 Wiley Periodicals, Inc. |
Affiliation:
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Cardiovascular Division, Department of Medicine Cardiovascular Research Center Department of Biomedical Engineering Department of Pediatrics, University of Virginia Medical Center, Charlottesville, Virginia, USA Division of Nephrology and Center of Translational Medicine, Department of Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, USA Department of Molecular Physiology and Biological Physics, University of Virginia Medical Center, Charlottesville, Virginia, USA. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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