青蒿素对克隆的内向整流钾通道的抑制作用(英文)

Inhibitory effect of artemisinin on cloned inward rectifier potassium channels 1

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（Ｋｉｒ２．１）的影响． 当蛙卵注射Ｋｉｒ２．１ 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－ １４０，－ １３０和－ １２０ ｍ Ｖ 时， ５ 和５０ μｍ ｏｌ·Ｌ－ １ 的青蒿素可使Ｋｉｒ２．１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 ｍ Ｖ 时， ５ 和５０ μｍ ｏｌ·Ｌ－ １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． 青蒿素的抗心律失常作用与它阻断Ｋｉｒ２．１通道电流有关．

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.