Document Detail


Ischemia Induces Closure of Gap Junctional Channels and Opening of Hemichannels in Heart-derived Cells and Tissue.
MedLine Citation:
PMID:  21865853     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
Aim: Gap junction intercellular communication (GJIC) and hemichannel permeability may have important roles during an ischemic insult. Our aim was to evaluate the effect of ischemia on gap junction channels and hemichannels. Methods: We used neonatal rat heart myofibroblasts and simulated ischemia with a HEPES buffer with high potassium, low pH, absence of glucose, and oxygen tension was reduced by dithionite. Microinjection, western blot, immunofluorescence, cell viability and dye uptake were used to evaluate the effects induced by dithionite. Isolated perfused rat hearts were used to analyse infarct size. Results: Short period with simulated ischemia reduced the ability to transfer a dye between neighbouring cells, which indicated reduced GJIC. Prolonged exposure to simulated ischemia caused opening of hemichannels, and cell death was apparent while gap junction channels remained closed. Connexin 43 became partially dephosphorylated and the total amount decreased during simulated ischemia. We were not able to detect the alternative hemichannel-forming protein, Pannexin 1, in these cells. The potential importance of Connexin 43 or Pannexin 1 hemichannels in ischemia-induced infarct in the intact heart was studied by perfusion of the heart in the presence of peptides that block one or the other type of hemichannels. The connexin-derived peptide, Gap26, significantly reduced the infract/risk zone ratio (control 48.7±4.2% and Gap26 19.4±4.1%, p<0.001), while the pannexin-derived peptide, (10)Panx1, did not change infarct/risk ratio. Conclusion: Connexin 43 is most likely responsible for both closure of gap junction channels and opening of hemichannels during simulated ischemia in neonatal rat heart myofibroblasts. Opening of connexin 43 hemichannels during ischemia-reperfusion seems to be an important mechanism for ischemia-reperfusion injury in the heart. By preventing the opening of these channels during early ischemia-reperfusion the infarct size becomes significantly reduced.
Authors:
David Johansen; Véronique Cruciani; Rune Sundset; Kirsti Ytrehus; Svein-Ole Mikalsen
Related Documents :
24400283 - Right ventricular failure and pathobiology in patients with congenital heart disease - ...
16939673 - Treatment of athletes with cardiac disease or arrhythmias.
2523983 - The impact of interventional techniques on the practice of cardiology.
Publication Detail:
Type:  Journal Article     Date:  2011-08-16
Journal Detail:
Title:  Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology     Volume:  28     ISSN:  1421-9778     ISO Abbreviation:  Cell. Physiol. Biochem.     Publication Date:  2011  
Date Detail:
Created Date:  2011-08-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9113221     Medline TA:  Cell Physiol Biochem     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  103-14     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 S. Karger AG, Basel.
Affiliation:
Cardiovascular Research Group, Department of Medical Biology, Faculty of Health Sciences, University of Tromsø, Tromsø, Norway.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

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


Previous Document:  Potential Therapeutic Value of Antioxidants for Abnormal Prolongation of QT Interval and the Associa...
Next Document:  NF?B is an unexpected major mediator of interleukin-15 signaling in cerebral endothelia.