【摘要】 目的探讨钙释放通道稳定蛋白FK506结合蛋白12.6(FKBP12.6)基因转染对心力衰竭(简称心衰)心室肌细胞钙通道(ICaL)和钠-钙交换电流(INCX)的影响。方法用携带FKBP12.6基因的重组腺病毒Ad.FKBP12.6-GFP感染分离的心衰心室肌细胞,通过免疫荧光及激光共聚焦技术检测转基因的表达;采用全细胞膜片钳技术记录ICaL和INCX。结果①心衰心室肌细胞的FKBP12.6蛋白表达显著下调,Ad.FKBP12.6-GFP感染细胞的FK-BP12.6蛋白表达水平显著高于Ad.GFP感染细胞;②Ad.GFP组心室肌细胞的ICaL密度峰值较正常对照组显著降低(6.81±0.83pA/pFvs11.43±1.14pA/pF,P<0.01),而FKBP12.6基因转染细胞电流密度峰值较Ad.GFP组显著升高(9.60±1.09pA/pFvs6.81±0.83pA/pF,P<0.01);③Ad.GFP组心室肌细胞的INCX较正常对照组明显升高(P<0.01),FKBP12.6基因转染使心衰心室肌细胞的INCX显著降低(P<0.05)。结论FKBP12.6基因转染显著升高心衰心室肌细胞ICaL,并显著降低INCX,从而逆转心衰时上述离子通道电流的改变。更多还原

【Abstract】 Objective To study the effects of FKBP12.6 gene transfer on L-type Ca2+ current(ICaL)and sodium-calcium exchanger current(INCX)in isolated ventricular myocytes of heart failure rats.Methods FKBP12.6 gene was transfered into ventricular myocytes of rats with heart failure mediated by adenovirus.Immunofluorescenc analysis was used to reveale specific overexpression of FKBP12.6.The whole-cell patch-clamp recording technique was used to record calcium channel current and sodium-calcium exchanger current.Results ①FKBP12.6 protein expression in ventricular myocytes of heart failure rats was down-regulated significantly.Adenovirus mediated FKBP12.6 gene transfer resulted in FKBP12.6 overexpression.②L-type Ca2+ current was significantly decreased in Ad-GFP myocytes compared with normal control(peak pA/pF,6.81±0.83 vs 11.43±1.14,P<0.01).L-type Ca2+ current in Ad.FKBP12.6-GFP cardiomyocytes was increased significantly compared with Ad.GFP myocytes((peak pA/pF,9.60±1.09 vs 6.81 ± 0.83,P<0.01).③Na+/Ca2+ exchanger current in ventricular myocytes of heart failure rats was increased significantly than normal control.FKBP12.6 gene transfer resulted in significant decrease of Na+/Ca2+ exchanger current in heart failure cardiomyocytes.Conclusion FKBP12.6 gene transfer reverses the change of L-type Ca2+ current and sodium-calcium exchanger current in ventricular myocytes of rats with heart failure,therefore arising as a potential therapeutic way for ventricular arrhythmia with heart failure.更多还原