Document Detail


Transmural stretch-dependent regulation of contractile properties in rat heart and its alteration after myocardial infarction.
MedLine Citation:
PMID:  15498894     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The "stretch-sensitization" response is essential to the regulation of heart contractility. An increase in diastolic volume improves systolic contraction. The cellular mechanisms of this modulation, the Frank-Starling law, are still uncertain. Moreover, their alterations in heart failure remains controversial. Here, using left ventricular skinned rat myocytes, we show a nonuniform stretch-sensitization of myofilament activation across the ventricular wall. Stretch-dependent Ca2+ sensitization of myofilaments increases from sub-epicardium to sub-endocardium and is correlated with an increase in passive tension. This passive tension-dependent component of myofibrillar activation is not associated with expression of titin isoforms, changes in troponin I level, and phosphorylation status. Instead, we observe that stretch induces phosphorylation of ventricular myosin light chain 2 isoform (VLC2b) in sub-endocardium specifically. Thus, VLC2b phosphorylation could act as a stretch-dependent modulator of activation tuned within normal heart. Moreover, in postmyocardial infarcted rat, the gradient of stretch-dependent Ca2+ sensitization disappears associated with a lack of VLC2b phosphorylation in sub-endocardium. In conclusion, nonuniformity is a major characteristic of the normal adult left ventricle (LV). The heterogeneous myocardial deformation pattern might be caused not only by the morphological heterogeneity of the tissue in the LV wall, but also by the nonuniform contractile properties of the myocytes across the wall. The loss of a contractile transmural gradient after myocardial infarction should contribute to the impaired LV function.
Authors:
Olivier Cazorla; Szabolcs Szilagyi; Jean-Yves Le Guennec; Guy Vassort; Alain Lacampagne
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-10-21
Journal Detail:
Title:  FASEB journal : official publication of the Federation of American Societies for Experimental Biology     Volume:  19     ISSN:  1530-6860     ISO Abbreviation:  FASEB J.     Publication Date:  2005 Jan 
Date Detail:
Created Date:  2005-01-04     Completed Date:  2005-11-07     Revised Date:  2012-02-15    
Medline Journal Info:
Nlm Unique ID:  8804484     Medline TA:  FASEB J     Country:  United States    
Other Details:
Languages:  eng     Pagination:  88-90     Citation Subset:  IM    
Affiliation:
INSERM U-637, CHU Arnaud de Villeneuve, Montpellier, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Cardiac Myosins / metabolism
Contractile Proteins / metabolism*
Heart*
Heart Ventricles / cytology,  metabolism
Male
Muscle Proteins / metabolism
Myocardial Infarction / metabolism*
Myocardium / metabolism
Myocytes, Cardiac / metabolism
Myosin Light Chains / metabolism
Phosphorylation
Protein Isoforms / metabolism
Rats
Rats, Wistar
Ventricular Myosins / metabolism
Chemical
Reg. No./Substance:
0/Contractile Proteins; 0/Muscle Proteins; 0/Myosin Light Chains; 0/Protein Isoforms; 0/myosin light chain 2; EC 3.6.1.-/Cardiac Myosins; EC 3.6.1.-/Ventricular Myosins

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