Document Detail


Cardiac conduction is required to preserve cardiac chamber morphology.
MedLine Citation:
PMID:  20675583     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Electrical cardiac forces have been previously hypothesized to play a significant role in cardiac morphogenesis and remodeling. In response to electrical forces, cultured cardiomyocytes rearrange their cytoskeletal structure and modify their gene expression profile. To translate such in vitro data to the intact heart, we used a collection of zebrafish cardiac mutants and transgenics to investigate whether cardiac conduction could influence in vivo cardiac morphogenesis independent of contractile forces. We show that the cardiac mutant dco(s226) develops heart failure and interrupted cardiac morphogenesis following uncoordinated ventricular contraction. Using in vivo optical mapping/calcium imaging, we determined that the dco cardiac phenotype was primarily due to aberrant ventricular conduction. Because cardiac contraction and intracardiac hemodynamic forces can also influence cardiac development, we further analyzed the dco phenotype in noncontractile hearts and observed that disorganized ventricular conduction could affect cardiomyocyte morphology and subsequent heart morphogenesis in the absence of contraction or flow. By positional cloning, we found that dco encodes Gja3/Cx46, a gap junction protein not previously implicated in heart formation or function. Detailed analysis of the mouse Cx46 mutant revealed the presence of cardiac conduction defects frequently associated with human heart failure. Overall, these in vivo studies indicate that cardiac electrical forces are required to preserve cardiac chamber morphology and may act as a key epigenetic factor in cardiac remodeling.
Authors:
Neil C Chi; Markus Bussen; Koroboshka Brand-Arzamendi; Chunhua Ding; Jeffrey E Olgin; Robin M Shaw; Gail R Martin; Didier Y R Stainier
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-07-30
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  107     ISSN:  1091-6490     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  2010 Aug 
Date Detail:
Created Date:  2010-08-18     Completed Date:  2010-09-27     Revised Date:  2014-09-19    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  United States    
Other Details:
Languages:  eng     Pagination:  14662-7     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Animals, Genetically Modified
Connexins / classification,  genetics,  metabolism
Electrocardiography
Embryo, Mammalian / embryology,  metabolism,  physiology
Embryo, Nonmammalian / embryology,  metabolism,  physiology*
Gene Knockdown Techniques
Green Fluorescent Proteins / genetics,  metabolism
Heart / embryology,  physiology*
Heart Conduction System / physiology*
In Situ Hybridization
Mice
Mice, Knockout
Microscopy, Confocal
Molecular Sequence Data
Mutation
Myocardium / metabolism*
Phylogeny
Sequence Homology, Amino Acid
Zebrafish / embryology,  genetics,  metabolism
Zebrafish Proteins / genetics,  metabolism
Grant Support
ID/Acronym/Agency:
HD25331/HD/NICHD NIH HHS; HL074891/HL/NHLBI NIH HHS; HL094414/HL/NHLBI NIH HHS; HL54737/HL/NHLBI NIH HHS; R01 HL094414/HL/NHLBI NIH HHS; R01 HL094414-01A1/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/Connexins; 0/Zebrafish Proteins; 0/connexin 46; 147336-22-9/Green Fluorescent Proteins
Comments/Corrections

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


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