青蒿素对蛙卵表达的克隆内向整流钾电流的抑制作用

Inhibition of Artemisinin on Cloned inward Rectifier Potassium Channels Expressed in Xenopus Oocytes

采用分子生物学及膜片钳技术，观测了青蒿素对非洲蛙卵表达的克隆内向整流钾通道（Ｋｉｒ２．１）的影响。当灌注不同浓度青蒿素时，青蒿素呈剂量依赖关系降低Ｋｉｒ２．１钾通道在非洲蛙卵细胞膜的功能表达。青蒿素阻断Ｋｉｒ２．１钾通道亦呈电压依赖性。当指令电压为－１４０ｍＶ，－１３０ｍＶ和－１２０ｍＶ时，５μｍｏ１／Ｌ和５０μｍｏ１／Ｌ的青蒿素可使Ｋｉｋ２．１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－５０ｍＶ，－４０ｍＶ和－３０ｍＶ时，５μｍｏ１／Ｌ和５０μｍｏ１／Ｌ的青蒿素则使Ｋｉｒ２．１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Ｋｉｒ２．１通道的阻断作用在用正常灌注液冲洗后可恢复。结果表明，青蒿素的抗心律失常作用与其有效阻断Ｋｉｒ２．１通道电流有关。

The effect of artemisinin (Art) on cloned inward rectifier potassium channels expressed in Xenopus oocytes was examined using molecular biology and patch clamp technique. Art reduced the functional expression of Kir2.1 potassium channels in Xenopus oocytes in a dose dependent manner when the oocytes were perfused by Art in the different concentration after RNA injection. Art blocked the Kir2.1 channels also in voltage dependent fashion. When command voltage was -140mV, -130mV and -120mV, Art in 5μmol/L and 50μmol/L reduced the inward current through Kir2.1 by 14.2%, 34.5%; 12.0%, 24.6%; 4.3%, 19.1%, respectively. When command voltage was -50mV, -40mV and -30mV, Art in 5μmol/L and 50μmol/L increased the outward current through Kir2.1 by 22.2%, 72.2%; 28.0%, 80.0%; 24.1%, 69.0%, respectively. Art blockade on the Kir2.1 channels could be recovered after washing using normal perfusing solution. In summary, the antiarrhythmic action of Art appears to be caused by its potent and distinct ability for blocking Kir2.1 channels.