[Role of gap junction in ischemic preconditioning].
OBJECTIVE
To investigate the role of gap junction in ischemic preconditioning (IPC).


METHODS
Sprague-Dawley rats were subjected to a 30 min coronary artery occlusion followed by 4 h of reperfusion (I/R). Rats were divided into seven groups: I/R, IPC/R, IPC/R + 5-hydroxydecanoic acid (mitochondrial ATP sensitive potassium channel antagonist), I/R + diazoxide (mitochondrial ATP sensitive potassium channel agonist), I/R + 5-hydroxydecanoic acid + diazoxide, I/R + 18beta-glycyrrhetinic acid (gap junction blocker) and I/R + 18beta-glycyrrhetinic acid + 5-hydroxydecanoic acid. Hemodynamics and myocardial infarct size were measured and connexin43 phosphorylation and subcellular distribution were determined by quantitative immunoblotting and confocal immunofluorescence.


RESULTS
Infarct size was reduced in IPC/R, I/R + diazoxide and I/R + 18beta-glycyrrhetinic acid group (13.34% +/- 7.87%, 11.02% +/- 2.24%, and 15.03% +/- 11.35%, respectively; P < 0.001 vs. I/R group: 45.81% +/- 7.91%). 5-hydroxydecanoic acid abolished the cardioprotective effects of IPC and diazoxide (46.57% +/- 5.36% and 47.36% +/- 3.17%; P > 0.05 vs. I/R) but not the effects of glycyrrhetinic acid (14.60% +/- 7.36%; P < 0.001 vs. I/R). Phosphorylation of connexin43 was significantly increased, dephosphorylation and connexin43 intracellular redistribution significantly decreased (Cx43 size in the cellular membrane 1.00% +/- 0.35% and 0.83% +/- 0.31%, P < 0.001 vs. I/R: 0.19% +/- 0.06%) by IPC and diazoxide and these effects could be abolished by 5-hydroxydecanoic acid.


CONCLUSIONS
Ischemic preconditioning could reduce myocardial infarction size by activating mitochondrial ATP sensitive potassium channel and modulating connexin43 phosphorylation and internalization.
Su
De-chun
DC
Department of Cardiology, First Affiliated Hospital of Dalian Medical University, Dalian 116011, China.
Chang
Zhi-wen
ZW
Fan
Shu-ying
SY
D000818:Animals; D018031:Connexin 43 / Q000378:metabolism; D017629:Gap Junctions / Q000502:physiology*; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism / Q000473:pathology; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley
D018031:Connexin 43