Document Detail

Effects of substitution of Cx43 by Cx32 on myocardial energy metabolism, tolerance to ischaemia and preconditioning protection.
MedLine Citation:
PMID:  20156849     Owner:  NLM     Status:  MEDLINE    
Connexin 43 (Cx43) plays an important role in cardioprotective signalling by mechanisms at least in part independent of gap junctional communication. To investigate whether this role is related to specific properties of this connexin isoform, we used a knock-in mouse model in which the coding region of Cx43 is replaced by that of Cx32. Homozygous Cx43KI32 mice showed reduced cell-to-cell Lucifer Yellow transfer (P < 0.01), but QRS duration and left ventricular fractional shortening (echocardiography) were similar to those in wild-type animals. NMR spectroscopy detected reduced ATP and increased lactate content in myocardium from homozygous Cx43KI32 animals (P < 0.05). Despite this, isolated homozygous Cx43KI32 hearts showed smaller infarcts after ischaemia-reperfusion (40 min/60 min) as compared to hearts from heterozygous and wild-type animals (13 and 31% reduction, respectively, P < 0.05). Cardiac myocytes isolated from Cx43KI32 mouse hearts also showed a reduced rate of cell death after simulated ischaemia-reperfusion. In a separate series of experiments, both ischaemic (4 cycles of 3.5 min of ischaemia and 5 min of reperfusion) and pharmacological (50 micromol l(-1) diazoxide, 10 min) preconditioning reduced infarct size in hearts from wild-type mice (by 24.84 and 26.63%, respectively, P < 0.05), but only ischaemic preconditioning was effective in hearts from heterozygous animals and both preconditioning strategies failed to protect Cx43KI32 homozygous hearts. These results demonstrate that Cx43 has an important and previously unknown modulatory effect in myocardial energy metabolism and tolerance to ischaemia, and plays a critical role in preconditioning protection, by mechanisms that are specific for this connexin isoform.
Antonio Rodríguez-Sinovas; Jose A Sánchez; Alejandra González-Loyola; Ignasi Barba; Miriam Morente; Rio Aguilar; Esperanza Agulló; Elisatet Miró-Casas; Neus Esquerda; Marisol Ruiz-Meana; David García-Dorado
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-02-15
Journal Detail:
Title:  The Journal of physiology     Volume:  588     ISSN:  1469-7793     ISO Abbreviation:  J. Physiol. (Lond.)     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-02     Completed Date:  2010-06-28     Revised Date:  2013-05-30    
Medline Journal Info:
Nlm Unique ID:  0266262     Medline TA:  J Physiol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1139-51     Citation Subset:  IM    
Laboratorio de Cardiología Experimental, Servicio de Cardiología, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
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MeSH Terms
Connexin 43 / genetics,  physiology*
Connexins / genetics,  physiology
Diazoxide / pharmacology
Energy Metabolism*
Gene Knock-In Techniques
Ischemic Preconditioning, Myocardial*
Mice, Transgenic
Myocardial Infarction / etiology,  pathology,  physiopathology*
Myocardial Reperfusion Injury / complications,  physiopathology*
Myocardium / metabolism*
Myocytes, Cardiac / drug effects,  metabolism
Reg. No./Substance:
0/Connexin 43; 0/Connexins; 0/connexin 32; 364-98-7/Diazoxide

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

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