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          Institute: MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut)     Collection: Publikationen des W. G. Kerckhoff-Instituts     Display Documents

ID: 275455.0, MPI für Herz- und Lungenforschung (W. G. Kerckhoff Institut) / Publikationen des W. G. Kerckhoff-Instituts
Gap junctional remodeling by hypoxia in cultured neonatal rat ventricular myocytes
Authors:Zeevi-Levin, N.; Barac, Y. D.; Reisner, Y.; Reiter, I.; Yaniv, G.; Meiry, G.; Abassi, Z.; Kostin, S.; Schaper, J.; Rosen, M. R.; Resnick, N.; Binah, O.
Date of Publication (YYYY-MM-DD):2005-04-01
Title of Journal:Cardiovasc Res
Journal Abbrev.:Cardiovasc Res
Issue / Number:1
Start Page:64
End Page:73
Audience:Not Specified
Abstract / Description: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.
Free Keywords:Animals Animals, Newborn Anoxia/*metabolism Arrhythmia/*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 Rats, Sprague-Dawley Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Reverse Transcriptase Polymerase Chain Reaction Time Factors
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für physiologische und klinische Forschung
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