普罗帕酮、胺碘酮、地尔硫卓对Kvl．4△N钾通道的作用

Effects of Propafenone, Amiodarone and Dflthiazem on the potassium channel of c-Type Kvl. 4△N

目的探讨不同类别抗心律失常药物普罗帕酮、胺碘酮和地尔硫卓对去N端Kvl．4通道（Kvl．4△N）的作用方式，以及这些作用的差异性。方法将Kvl．4△N的mRNA注射入非洲爪蟾卯母细胞并使用双电极钳制法（two electrodes voltage clamp，TEV），运用Clampfit9．0软件分别观察三种药物对KVl．4△N电生理特性的影响。结果三种药物对fKvl．4△N通道的作用都具有浓度、频率和电压依赖性。在亲和力方面，propafenone的IC50最小，dilthiazem次之，arniodarone的IC50最大（P=0．031）；在频率抑制性方面，propafenone组达到稳态时为对照组的41％，amiodarone为32％左右，dilthiazem为21％左右（P=0．045）；在电压抑制性方面，100μMpropafenone，500μMamiodarone、350μMdihhiazem在＋50mV电压下分别能使fKvl．4△N通道电流抑制到对照组的（54．6±1．9）％，（46．34-3．5）％和（52．8±2．8）％（P=0．046）。结论三者都是fKvl．4△N通道的开放通道阻滞剂，对fKvl．4△N通道的作用和机制既有相同之处，又有不同特点，这可能是三者抗心律失常的机制之一。

Objective To study the effects of the antiarrhythmic drugs of propafenone, amiodarone and difthiazem on c-type Kvl. 4 channels in Xenopus laevis oocytes with two-electrode voltage-clamp technique. Methods Defolliculated oocytes （stage V - VI） had transcribed cRNAs of ferret Kvl. 4△N channels injected. The oocytes were continuously perfused with control solution or propafenone, amiodarone and dilthiazem under monitoring of software of Clampfit v 9. 0. Results All of the three drugs blocked ferret Kvl. 4△N channel in voltage-, frequency- and concentration-dependent manners. The values of IC50 （50% inhibiting concentration ） of propafenone, amiodarone and dilthiazem were （ 103.4±2. 2 ） μmol/L, （501.22± 5.9） μmol/L and （353.62 ± 9.9） μmot/L, respectively. The currents under the actions of propafenone , amiodarone and dilthiazem were decreased to 41%, 32% and 21% of control group, respectively. Propafenone （100μmol/L）, Amiodarone （500μmol/L）, dilthiazem （350μmol/L） inhibited currents to （54. 6 ±1.9 ） %, （ 46. 3 ± 3.5 ） % , （ 52. 8 ± 2. 8 ） % of control group in voltage-dependent blockage. Conclusions The results suggested that all the three drugs blocked the kvl. 4△N channel in the open state. The three drugs block the kvl. 4△N channel maybe had the similiar effects in some respects, but each had its unique characteristics.