Document Detail

Gap junctional remodeling by hypoxia in cultured neonatal rat ventricular myocytes.
MedLine Citation:
PMID:  15769449     Owner:  NLM     Status:  MEDLINE    
OBJECTIVES: Altered gap junctional coupling of ventricular myocytes plays an important role in arrhythmogenesis in ischemic heart disease. Since hypoxia is a major component of ischemia, we tested the hypothesis that hypoxia causes gap junctional remodeling accompanied by conduction disturbances. METHODS: Cultured neonatal rat ventricular myocytes were exposed to hypoxia (1% O(2)) for 15 min to 5 h, connexin43 (Cx43) expression was analyzed, and conduction velocity was measured using the Micro-Electrode Array data acquisition system. RESULTS: After 15 min of hypoxia, conduction velocity was unaffected, while total Cx43, including the phosphorylated and nonphosphorylated isoforms, was increased. After 5 h of hypoxia, total Cx43 protein was decreased by 50%, while the nonphosphorylated Cx43 isoform was unchanged. Confocal analyses yielded a 55% decrease in the gap junctional Cx43 fluorescence signal, a 55% decrease in gap junction number, and a 26% decrease in size. The changes in Cx43 were not accompanied by changes in mRNA levels. The reduction in Cx43 protein levels was associated with a approximately 20% decrease in conduction velocity compared to normoxic cultures. CONCLUSIONS: Short-term hypoxia (5 h) decreases Cx43 protein and conduction velocity, thereby contributing to the generation of an arrhythmogenic substrate.
Naama Zeevi-Levin; Yaron D Barac; Yotam Reisner; Irina Reiter; Gal Yaniv; Gideon Meiry; Zaid Abassi; Sawa Kostin; Jutta Schaper; Michael R Rosen; Nitzan Resnick; Ofer Binah
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Cardiovascular research     Volume:  66     ISSN:  0008-6363     ISO Abbreviation:  Cardiovasc. Res.     Publication Date:  2005 Apr 
Date Detail:
Created Date:  2005-03-16     Completed Date:  2005-08-05     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0077427     Medline TA:  Cardiovasc Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  64-73     Citation Subset:  IM    
Rappaport Faculty of Medicine, Technion, Haifa, Israel.
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MeSH Terms
Animals, Newborn
Anoxia / metabolism*
Arrhythmias, Cardiac / metabolism*,  physiopathology
Blotting, Western / methods
Connexin 43 / analysis,  genetics,  metabolism
Gap Junctions / chemistry,  metabolism*
Heart Conduction System
Heart Ventricles
Immunohistochemistry / methods
Microscopy, Confocal
Myocytes, Cardiac / chemistry,  metabolism*
RNA, Messenger / analysis
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Time Factors
Reg. No./Substance:
0/Connexin 43; 0/RNA, Messenger
Comment In:
Cardiovasc Res. 2005 Apr 1;66(1):9-11   [PMID:  15769443 ]

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