Ischemia enhances translocation of connexin43 and gap junction intercellular communication, thereby propagating contraction band necrosis after reperfusion

Abstract

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. Methods and 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 1,000xg 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.