Ischemia enhances translocation of connexin43 and gap junction intercellular communication, thereby propagating contraction band necrosis after reperfusion.
BACKGROUND
In ischemia-reperfusion, contraction band necrosis (CBN) is distributed mainly to the lateral border of the risk area and does not spread into the non-risk area beyond the border. It has been suggested that CBN is propagated through gap junctions (GJs), but it is unclear how GJs transmit CBN exclusively in the risk area.


RESULTS
Coronary occlusion for 30 min in rat increased the level of connexin43 (Cx43) protein in the 100,000 x g pellet fraction to 1.5-fold and decreased that in the 1,000 x g pellet to half in the risk area compared with the non-risk area. Immunohistochemical analysis showed an increase of Cx43 at intercalated disks in the risk area. A dye transfer assay demonstrated enhancement of GJ intercellular communication (GJIC) in the risk area compared with the non-risk area in the same section. Administration of a GJ blocker, carbenoxolone, at the onset of reperfusion following 30 min of ischemia reduced the CBN area (1/3 vs PBS) in 5 min of reperfusion and limited the infarct size (2/3 vs PBS) in 6 h of reperfusion.


CONCLUSIONS
These data suggest that ischemia enhances translocation of Cx43 to GJs, thereby promoting propagation of CBN exclusively in the risk area through enhanced GJIC after reperfusion.
Shintani-Ishida
Kaori
K
Department of Forensic Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. kaori@m.u-tokyo.ac.jp
Unuma
Kana
K
Yoshida
Ken-ichi
K
D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects; D018031:Connexin 43 / Q000378:metabolism*; D004195:Disease Models, Animal; D017629:Gap Junctions / Q000187:drug effects / Q000378:metabolism*; D054061:Ischemic Contracture / Q000378:metabolism / Q000473:pathology; D008297:Male; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D017202:Myocardial Ischemia / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009336:Necrosis; D010766:Phosphorylation; D021381:Protein Transport; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D015854:Up-Regulation
D018031:Connexin 43; D002229:Carbenoxolone