青蒿素对克隆的内向整流钾通道的抑制作用

采用双电极电压钳技术观测了青蒿素对表达于非洲蛙卵的克隆内向整流钾通道(K_ir2.1)的影响. 当蛙卵注射K_ir2.1 cRNA后灌注不同浓度青蒿素时, 青蒿素呈浓度依赖关系降低K_ir2.1钾通道在非洲蛙卵细胞膜的功能表达. 青蒿素阻断K_ir2.1钾通道亦呈电压依赖性. 当指令电压为-140, -130和-120 mV时, 5和50 μmol·L^-1的青蒿素可使K_ir2.1钾通道的内向电流分别下降14.2%, 34.5%; 12.0%, 24.6%; 4.3%, 19.1%. 当指令电压为-50, -40和-30 mV时, 5和50 μmol·L^-1的青蒿素则使K_ir2.1钾通道的外向电流分别增加22.2%, 72.2%; 28.0%, 80.0%; 24.1%, 69.0%. 青蒿素对K_ir2.1通道的阻断作用在用正常灌注液冲洗后可恢复. 青蒿素的抗心律失常作用与它阻断K_ir2.1通道电流有关.

Inhibitory effect of artemisinin on cloned inward rectifier potassium channels

The effect of artemisinin (Art) on one of major types of cloned inward rectifier potassium channel(K_ir2.1 channel) expressed in Xenopus oocytes was examined using a two electrode voltage clamp. Art reduced the functional expression of K_ir2.1 channels in Xenopus oocytes in a concentraction- dependent manner when the oocytes were perfused by Art after cRNA injection. Art blocked the K_ir2.1 channels also in voltage-dependent fashion. When command voltage was -140, -130 and -120 mV, Art in 5 and 50 μmol·L^-1 reduced the inward current through K_ir2.1 channel by 14.2%, 34.5%; 12.0%, 24.6%; 4.3%, 19.1%, respectively. When command voltage was -50, -40 and -30 mV, Art in 5 and 50 μmol·L^-1 increased the outward current through K_ir2.1 channel by 22.2%, 72.2%; 28.0%, 80.0%; 24.1%, 69.0%, respectively. The blockade of Art on the K_ir2.1 channels was recovered after washing using normal perfusing solution. The results suggest that the antiarrhythmic action of Art is caused by its blocking effect on K_ir2.1 channels.