地高辛衍生物对人胚肾细胞293延迟整流钾电流的作用

Study on delayed after potassium current in human embryonic kidney 293 cell with digoxin derivatives

目的研究地高辛衍生物对人胚肾细胞(human embryonic kidney 293 cell,HEK-293)上延迟整流钾电流(delayed after potassium current,I_K)的影响。方法应用磷酸钙瞬时转染的方法,将人心肌细胞上的延迟整流钾电流通道蛋白基因(human Ether-a-go-go Related Gene,HERG)转染进人胚肾细胞,全细胞膜片钳技术记录药物浓度分别为1、10、100 nmol·L^(-1)的地高辛甲、乙两种衍生物对人胚肾细胞上HERG钾通道时间依赖性电流(I_(step))和尾电流(I_(tail))的影响。结果地高辛衍生物甲和地高辛类似,对HERG钾通道时间依赖性电流和尾电流均呈现剂量依赖性抑制,其半数最大抑制浓度IC_(50)分别为20.61、22.69 nmol·L^(-1);未见地高辛衍生物乙对HERG钾通道延迟整流钾电流的抑制作用。结论地高辛衍生物甲对转染HERG钾通道的人胚肾细胞的延迟整流钾电流呈浓度依赖性抑制;而地高辛衍生物乙对转染HERG钾通道的人胚肾细胞的延迟整流钾电流无抑制作用。

Objective To investigate the effects of digoxin derivatives on delayed after potassium current( IK) in human embryonic kidney 293cell( HEK- 293). Methods The human Ether- a- go- go Related Gene( HERG) was transfected into HEK- 293 cells by using calcium phosphate transfection method,the effects of different concentrations of 1,10,100nmol·L^(-1)digoxin derivatives A and derivatives B on the time dependent currents( I_(step)) and tail currents( I_(tail)) of HERG potassium channels were recorded by whole cell patch clamp technique. Results The HERG potassium channel Istepand Itailwere showed dose dependent inhibition by digoxin derivatives A,the half maximal inhibitory concentration( IC_(50)) were20. 61 and 22. 69 nmol·L^(-1). Digoxin derivatives B had no inhibition on HERG potassium channel IK. Conclusion The IK of HERG potassium channels in HEK- 293 cells was inhibited by digoxin derivatives A in a concentration dependent manner,while digoxin derivatives B have no inhibition to this.