Effect of γ-glutamyl transpeptidase on Ito channel remodeling in rat heart post-myocardial infarction

Objective:To identify whether GGT activity is relative to Kv channel remodeling in post-myocardial infarction.Method:We selected 180-200 g male SD rats to establish myocardial infarction(MI) model(MI group),and control group that have the same operation with the MI group but without ligation of coronary artery.6-8 weeks after operation,we extracted cell membrane proteins of myocardium,then analyzed GGT activity with biological chemical method,dected GGT mRNA expression with Real Time PCR,and tested GGT protein expression with Western blotting.Single ventricular myocytes were obtained by enzymatic method,and Ito was recorded by whole cell patch clamp technique.Result:①Compared with control group,GGT activity in MI group increased significantly(left ventricular increased 45%,ventricular septal increased 31%),while expressions of GGT mRNA and protein increased significantly too.②The density of Ito decreased significantly in MI group than that in control group [(16.2±3.1)pA/pF vs(30.9±3.8)pA/pF,P0.05],then was recovery to the level of control group after preconditioning with GSHo in 4~5 h [(30.1±3.3)pA/pF vs(30.9±3.8)pA/pF,P0.05].③The functions of GGT specific blockers on Ito density were completely inhibited by GSHo,but the effect of NAC on Ito density didn′t affected by GSHo.Conclusion:GGT mediates the remodling effect of GSHo on Ito channels.The catalytic decomposition of GGT could be used as a clinical treatment strategy to reverse cardiac electrical remodeling.