重金属镉(Cd)污染及其对动植物的伤害机理,已成为中外相关专家研究的热点,但是细胞毒害机理依然不清楚.分布于细胞膜上的通道蛋白,不仅是外来物质作用于生物体的首要位点,且会影响离子通道的功能.为阐释镉(Cd)污染致病与毒害的细胞学机理,选择具有重要生理功能的细胞钾离子(K+)通道为示踪,并应用全细胞膜片钳技术,研究了Cd2+对hERG(K+)通道电流的影响.结果表明:(1)Cd^2+能显著抑制hERGK+通道的稳态电流和尾电流,干扰通道蛋白正常开关;(2)当10,50,200μg/LCd^2+作用细胞后,hERG(K+)通道激活曲线右移,斜率因子不变;(3)当10μg/Lcd^2+作用细胞后,hERGK+通道电流迅速下降,且随Cd^2+浓度增加,此抑制作用未发生明显改变.本工作从一新的角度揭示了Cd^2+细胞毒性机理.结果提示,钾通道可作为镉污染致病与毒害的细胞学机理研究的靶点.
Cadmium (Cd) contamination leads to a variety of clinical diseases. Potassium ion (K+) channel is the most diverse and ubiquitous class of ion channels, and it plays the important physiological roles in human. In order to elucidate the cellular mechanism of the pathogenic and toxic effect of Cd^2+pollution, the effects of Cd^2+on the currents of a human ether-a-go-go related gene (hERG) K+channel was investigated by a whole-cell patch clamp method. The results indicated that Cd^2+ significantly inhibited the steady-state and tail currents of hERG K+channel. When cells were treated with 10, 50, 200 μg/L Cd^2+, the activation curve of hERG K+channel was right-shifted, and the slope factor was not changed. The currents of hERG K+ channel was not significantly changed with increasing the concentration of Cd^2+. The results suggested that potassium channels can be used as the target of the research on the cellular mechanism of the pathogenic and toxic effect of Cd^2+pollution.