Document Detail


Phospholemman deficiency in postinfarct hearts: enhanced contractility but increased mortality.
MedLine Citation:
PMID:  22686200     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-03-27
Journal Detail:
Title:  Clinical and translational science     Volume:  5     ISSN:  1752-8062     ISO Abbreviation:  Clin Transl Sci     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-06-12     Completed Date:  2012-10-04     Revised Date:  2014-01-27    
Medline Journal Info:
Nlm Unique ID:  101474067     Medline TA:  Clin Transl Sci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  235-42     Citation Subset:  IM    
Copyright Information:
© 2012 Wiley Periodicals, Inc.
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MeSH Terms
Descriptor/Qualifier:
Animals
Calcium Signaling
Cell Size
Heart Function Tests
Ion Channel Gating
Membrane Proteins / deficiency*,  metabolism
Mice
Mice, Inbred C57BL
Mice, Knockout
Models, Cardiovascular
Myocardial Contraction / physiology*
Myocardial Infarction / metabolism*,  pathology,  physiopathology*,  ultrasonography
Myocardium / metabolism*,  pathology*
Myocytes, Cardiac / pathology
Organ Size
Phosphoproteins / deficiency*,  metabolism
Phosphorylation
Sodium-Potassium-Exchanging ATPase / metabolism
Survival Analysis
Grant Support
ID/Acronym/Agency:
R01 HL074854/HL/NHLBI NIH HHS; R01-HL-58672/HL/NHLBI NIH HHS; R01-HL-69074/HL/NHLBI NIH HHS; R01-HL-74854/HL/NHLBI NIH HHS; T32-HL007355-26/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Membrane Proteins; 0/Phosphoproteins; 135541-82-1/phospholemman; EC 3.6.3.9/Sodium-Potassium-Exchanging ATPase
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