依托咪酯对HEK-293细胞中异源表达的hERG钾通道电流的抑制作用*
Inhibition effects of etomidate on hERG K+ channel expressed in HEK-293 cells

目的:观察依托咪酯对HEK-293细胞中异源表达的hERG钾通道电流的抑制作用及其机制。方法:采用脂质体瞬时转染的方法将野生型hERG(WT-hERG)、突变型Y652A-hERG和F656C-hERG分别转染人胚胎肾细胞HEK-293,应用全细胞膜片钳技术记录依托咪酯对转染后HEK-293细胞表达的hERG钾通道电流的抑制作用以及对激活曲线和失活曲线的影响。结果:依托咪酯可浓度依赖性地抑制WT-hERG转染的HEK-293细胞钾通道电流,其半数最大抑制浓度为(6.41±2.43)μmol/L,对激活曲线和失活曲线无明显影响。与WT-hERG转染的HEK-293细胞相比,依托咪酯对突变体Y652A-hERG及F656C-hERG转染的HEK-293细胞内钾通道电流的抑制作用减弱。结论:F656C可能是依托咪酯抑制hERG钾通道的重要靶点。
Aim: To investigate the molecular mechanisms of etomidate on hERG K+ channel expressed in human embryonic kidney(HEK-293)cells.Methods: HEK-293 cells were transfected transiently with different hERG plasmid(WT, mutant Y652A and F656C, respectively)using lipofection. Whole-cell patch clamp technique was used to record the effects of etomidate on hERG K+ channel current,and the activation and inactivation curves expressed in HEK-293 cells.Results: Etomidate directly inhibited WT-hERG K+ current in a concentration-dependent manner, and half-maximum block concentration was(6.41±2.43)μmol/L. But etomidate did not markedly modify the activation and inactivation curves of WT-hERG K+ channel. The inhibition effects of etomidate on mutant Y652A-hERG and F656C-hERG K+ channel were attenuated compared with WT-hERG K+ channel.Conclusion: F656C may be the key target that etomidate inhibits the hERG K+ channel