| Objective: P38 kinase is a key regulator of apoptosis.Especially in cardiac hypertrophy and necrosis caused by pathological stress.,but its role in regulating ion channels remodeling is unclear.So the purpose of this study is to further clarify the role of p38 kinase signaling pathway in the regulation of voltage gated potassium channels(Kv)in rats with myocardial infarction(MI)after 6-8 weeks.Methods: Male Sprague-Dawley(SD)rats were purchased from the experimental animal center of Hebei Medical University.All animal procedures were carried out in accordance with guidelines approved by the University of He Bei Medical Institutional Animal Care.Male Sprague–Dawley rats(180~200g)were established model of myocardial infarction.During 6-8 weeks after surgery,the rats were anesthetized and the heart was isolated from the chest.Hearts were excised and perfused via the coronary vasculature by the Langendorff method.SingleMyocytes were dissociated from perfused hearts by a collagenase digestion procedure described previously,and were incubated in 95%?C and5% O2 for 4.5h.Using cell patch clamp technique to analyze the sample voltage gated potassium channel(Kv)and Ito.P38 kinase activity was detected using a nonradioactive p38 kinase assay kit(cell signaling technique).Results:1 The p38 activity of the myocardium after myocardial infarction was detected by Western blot,which increased about 2-6 times compared with that in the control group.(Control:2.0±1.1,n=6;MI:7.2±1.7,n=6;P<0.05).2 When post-MI myocytes were treated with p38 inhibitors SB203580 15 ?M for 4-5h,Ito density obviously increased.(SB203580+MI : 25.6±1.0 pA/pF,n=10;MI ?:15.9±2.1 pA/pF,n=10;P<0.05).3 Trx reductase inhibitor auranofin(AF,1?M)significantly inhibited the effect of SB203580 on the myocardial Ito current in rats with myocardial infarction(MI+AF+ SB203580:0.5±0.1,n=10),while AF did not change the Ito density of control heart.Insulin like growth factor(IGF-1)can significantly enhance the role of Trx,and increase the intensity of Ito current.4 Western blot analysis showed that the expression of Kv4.2 channel protein was significantly increased after with p38 inhibitor SB203580,although not to the level of control hearts.These findings agreewith the upregulation of Ito density observed in isolated MI myocytes.There was no significant change in the expression of Kv4.2 protein in the myocardium of control group after SB203580 treatment.Conclusion: The change of potassium channel in myocardial ischemia caused by ischemic necrosis is able to regulate,which can promote the change of potassium channel by activating the p38 signaling pathway,which leads to the change of Ito.This process can be regulated by IGF-1 and Trx.The results of this study showed that in myocardial infarction,p38 kinase activity was significantly enhanced,to further reduce the Ito current intensity of Kv channel mediated;inhibition of the p38 signaling pathway can significantly increase the expression of Kv channel protein,and then improve the Ito current intensity,this process can be Trx,IGF-1 control system. |
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