Role of gap junction in ischemic preconditioning / 中华心血管病杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the role of gap junction in ischemic preconditioning (IPC).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>Ischemic preconditioning could reduce myocardial infarction size by activating mitochondrial ATP sensitive potassium channel and modulating connexin43 phosphorylation and internalization.</p>