Wu S N, Lo Y K, Chen H, Li H F, Chiang H T
Department of Medical Education and Research, Kaohsiung Veterans General Hospital, 386 Ta-Chung 1st Road, 813, Kaohsiung, Taiwan.
Neuropharmacology. 2001 Dec;41(7):834-43. doi: 10.1016/s0028-3908(01)00114-9.
The effects of rutaecarpine on ionic currents of NG108-15 neuronal cells were investigated in this study. Rutaecarpine (2-100 microM) suppressed the amplitude of delayed rectifier K+ current (I(K(DR))) in a concentration-dependent manner. The IC50 value for rutaecarpine-induced inhibition of I(K(DR)) was 11 microM. I(K(DR)) present in these cells is sensitive to the inhibition by quinidine and dendrotoxin, yet not by E-4031. The presence of rutaecarpine enhanced the rate and extent of I(K(DR)) inactivation, although it had no effect on the initial activation phase of I(K(DR)). Recovery from block by rutaecarpine (5 microM) was fitted by a single exponential with a value of 2.87 s. Crossover of tail currents in the presence of rutaecarpine was also observed. Cell-attached single-channel recordings revealed that rutaecarpine decreased channel activity, but it did not alter single-channel amplitude. With the aid of the binding scheme, a quantitative description of the rutaecarpine actions on I(K(DR)) was provided. However, rutaecarpine (20 microM) had no effect on L-type Ca2+ current. Under current-clamp configuration, rutaecarpine prolonged action potential duration in NG108-15 cells. These results show that rutaecarpine is a blocker of the K(DR) channel. The increase in action potential duration induced by rutaecarpine can be explained mainly by its blocking actions on I(K(DR)).
本研究考察了吴茱萸次碱对NG108 - 15神经细胞离子电流的影响。吴茱萸次碱（2 - 100微摩尔）以浓度依赖性方式抑制延迟整流钾电流（I(K(DR))）的幅度。吴茱萸次碱诱导I(K(DR))抑制的IC50值为11微摩尔。这些细胞中存在的I(K(DR))对奎尼丁和树眼镜蛇毒素的抑制敏感，但对E - 4031不敏感。吴茱萸次碱的存在增强了I(K(DR))失活的速率和程度，尽管它对I(K(DR))的初始激活阶段没有影响。从5微摩尔吴茱萸次碱的阻断中恢复符合单指数拟合，值为2.87秒。在存在吴茱萸次碱的情况下也观察到尾电流的交叉。细胞贴附式单通道记录显示，吴茱萸次碱降低了通道活性，但没有改变单通道幅度。借助结合模式，对吴茱萸次碱对I(K(DR))的作用进行了定量描述。然而，20微摩尔的吴茱萸次碱对L型钙电流没有影响。在电流钳模式下，吴茱萸次碱延长了NG108 - 15细胞的动作电位持续时间。这些结果表明，吴茱萸次碱是K(DR)通道的阻断剂。吴茱萸次碱诱导的动作电位持续时间增加主要可由其对I(K(DR))的阻断作用来解释。
