乌头碱阻断表达在卵母细胞上的HERG通道的电药理特性

目的观察乌头碱对表达在卵母细胞上的HERG电流的影响。方法HERG通道表达在非洲爪蟾卵母细胞上,利用双电极电压钳技术测量其电流。结果①HERG通道可以稳定表达在卵母细胞上;②乌头碱以浓度和电压依赖性方式阻断表达在卵母细胞上的野生型HERG通道,阻断的半数抑制浓度值是1.801±0.332μmol/L;③乌头碱对HERG电流的阻断呈时间依赖性;④峰电流幅值被1μmol/L乌头碱显著降低,而稳态失活的半数失活电压(-39.10±1.04 mV vs-41.61±2.66 mV,P>0.05,n=6)没有被乌头碱的阻断显著改变,而斜率k(32.37±1.04 mV vs 41.05±4.19 mV,P<0.05,n=6)出现正向移动。结论乌头碱对HERG电流呈浓度、电压和时间依赖性阻断,而其对失活状态下的HERG通道无明显阻断作用,HERG通道可能是乌头碱致心律失常的关键离子靶点之一。

Electropharmacological properties of acontine while blocking HERG potassium channels expressed on Xenopus laevis oocytes

Objective To investigate the inhibitory effect of acontine on human ether-a-go-go-related gene(HERG) channels expressed on Xenopus laevis oocytes.Methods HERG channels were expressed on Xenopus laevis oocytes and studied using two microelectrode voltage clamp technique.Results In HERG channels,acontine carried on a voltage-and concentration-dependent inhibition with IC50 of were 1.801±0.332 μmol/L.Acontine preferentially blocked the current of open-state HERG channel with a time-dependent way.On the other hand,the peak current was inhibited significantly by 1μmol/L of aconitine,but the half voltage(V1/2)of stable inactivation was not be impacted with a positive shift of the slope(k) of the stable inactive curve(-39.10±1.04 mV vs-41.61±2.66 mV,P>0.05,n=6).Conclusions Aconitine blocks HERG channel with a voltage-and concentration-and time-dependent pattern,but it does not inhibit the inactive channels.It can be conferred that HERG channel may be one of the key target sites of which aconitine effects on and accordingly induces arrhythmias.