Document Detail


Replacement of connexin40 by connexin45 in the mouse: impact on cardiac electrical conduction.
MedLine Citation:
PMID:  14630724     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Gap junction channels, required for the propagation of cardiac impulse, are intercellular structures composed of connexins (Cx). Cx43, Cx40, and Cx45 are synthesized in the cardiomyocytes, and each of them has a unique cardiac expression pattern. Cx40 knock-in Cx45 mice were generated to explore the ability of Cx45 to replace Cx40, and to assess the functional equivalence of these two Cxs that are both expressed in the conduction system. ECGs revealed that the consequences resulting from the biallelic replacement of Cx40 by Cx45 were an increased duration of the P wave, and a prolonged and fractionated QRS complex. Epicardial mapping indicated that the conduction velocities (CV) in the right atrium and the ventricular myocardium, as well as conduction through the AV node, were unaffected. The significant reduction of the CV in the left atrium would be the most likely cause of the P-wave lengthening. In the right ventricle, a changed and prolonged activation in sinus rhythm was found in homozygous mutant mice, which may explain the prolongation and splitting of the QRS complex. Electrical mapping of the His bundle branches revealed that this was due to slow conduction measured in the right branch. The CV in the left branch was unchanged. Therefore, in the absence of Cx40, the upregulation of Cx45 in the heart results in a normal impulse propagation in the right atrium, the AV node, and the left His bundle branch only.
Authors:
S?bastien Alcol?a; Th?r?se Jarry-Guichard; Jacques de Bakker; Daniel Gonz?lez; Wouter Lamers; Steven Coppen; Luis Barrio; Habo Jongsma; Daniel Gros; Harold van Rijen
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2003-11-20
Journal Detail:
Title:  Circulation research     Volume:  94     ISSN:  1524-4571     ISO Abbreviation:  Circ. Res.     Publication Date:  2004 Jan 
Date Detail:
Created Date:  2004-01-12     Completed Date:  2004-01-14     Revised Date:  2010-05-26    
Medline Journal Info:
Nlm Unique ID:  0047103     Medline TA:  Circ Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  100-9     Citation Subset:  IM    
Affiliation:
Laboratoire de G?n?tique et Physiologie du D?veloppement, UMR CNRS 6545, Institut de Biologie du D?veloppement de Marseille, Universit? de la M?diterran?e, Marseille, France.
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MeSH Terms
Descriptor/Qualifier:
Animals
Connexins / genetics*,  physiology*
Electric Conductivity
Electrocardiography
Heart Conduction System / physiology*
Mice
Mice, Transgenic
Myocytes, Cardiac / cytology,  metabolism
Protein Biosynthesis
Transcription, Genetic
Chemical
Reg. No./Substance:
0/Connexins; 0/connexin 40; 0/connexin 45
Comments/Corrections
Comment In:
Circ Res. 2004 Jan 9;94(1):4-6   [PMID:  14715530 ]

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


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