Document Detail


Extensible behavior of titin in the miniswine left ventricle.
MedLine Citation:
PMID:  20124120     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: The sarcomeric protein titin is a molecular spring responsible for passive tension and restoring forces of cardiomyocytes. Extension of titin as a function of sarcomere length (SL) has been studied in rodents, which predominantly express the smaller, stiffer N2B titin isoform. Large mammals coexpress roughly equal proportions of N2B and N2BA titin, the larger, more compliant isoform. We hypothesized that extension of titin in relation to SL differs in large mammals and that this difference is functionally important.
METHODS AND RESULTS: We characterized the filling pressure-SL relation in diastolic-arrested miniswine left ventricles. SL was 2.15 to 2.25 mum at a filling pressure of approximately 0 mm Hg and reached a maximum of approximately 2.50 mum with overfilling. In the normal filling pressure range, SL ranged from approximately 2.32 to approximately 2.40 mum. We assessed titin extension as a function of SL using immunoelectron microscopy, which allowed delineation of the behavior of specific spring segments. The major isoform difference was that the N2B-Us segment extended approximately 4-fold more as a function of SL in N2B compared with N2BA titin. Using this segment, we estimated sarcomeric force development with a worm-like chain model and found that N2B develops markedly greater force than N2BA titin. The resulting force with coexpression of N2B and N2BA titin is intermediate.
CONCLUSIONS: In light of murine studies showing that operating SLs are shorter than in miniswine, our results indicate that coexpression of the 2 titin isoforms in large mammals allows longer SLs without the development of excessive diastolic tension.
Authors:
Martin M Lewinter; Joseph Popper; Mark McNabb; Lori Nyland; Stephen B Bell; Henk Granzier
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2010-02-01
Journal Detail:
Title:  Circulation     Volume:  121     ISSN:  1524-4539     ISO Abbreviation:  Circulation     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-17     Completed Date:  2010-03-31     Revised Date:  2014-09-18    
Medline Journal Info:
Nlm Unique ID:  0147763     Medline TA:  Circulation     Country:  United States    
Other Details:
Languages:  eng     Pagination:  768-74     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Connectin
Diastole / physiology
Male
Microscopy, Immunoelectron
Models, Animal
Muscle Proteins / physiology*,  ultrastructure
Myocardial Contraction / physiology
Myocytes, Cardiac / physiology
Protein Isoforms
Protein Kinases / physiology*,  ultrastructure
Sarcomeres / physiology*,  ultrastructure
Swine
Swine, Miniature
Ventricular Function, Left / physiology*
Grant Support
ID/Acronym/Agency:
HL062881/HL/NHLBI NIH HHS; R01 HL061497/HL/NHLBI NIH HHS; R01 HL061497-05/HL/NHLBI NIH HHS; R01 HL062881/HL/NHLBI NIH HHS; R01 HL062881-09/HL/NHLBI NIH HHS; R01 HL61497/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Connectin; 0/Muscle Proteins; 0/Protein Isoforms; EC 2.7.-/Protein Kinases
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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