Wang Yu-Wen, Yang Chin-Tsang, Chen Yi-Hung, Gong Chi-Li, Chen Yu-Fang, Kuo Yueh-Hsiung, Leung Yuk-Man
Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung, Taiwan.
Lan Yang Institute of Technology, Yilan, Taiwan.
Pharmacol Rep. 2015 Feb;67(1):134-9. doi: 10.1016/j.pharep.2014.08.015. Epub 2014 Aug 27.
Imperatorin is a furocoumarin isolated from Angelica archangelica and Cnidium monnieri. It has multiple neuromodulatory actions such as anticonvulsant effects, anxiolytic effects and anti-nociceptive effects. Although there have been reports demonstrating its effects on voltage-gated Na(+) channels (VGSC) and transient reversal potential (TRP) V1 channels in neurons, there is hitherto no work showing whether this compound affects voltage-gated K(+) (Kv) channels and ATP-sensitive K(+) (KATP) channels.
We investigated the effects of imperatorin on K(+) channels using whole-cell configuration voltage-clamp technique.
Imperatorin inhibited Kv channels in differentiated neuronal NG108-15 cells, and caused a left shift in the steady-state inactivation curve without affecting activation gating. Imperatorin also inhibited heterologously expressed wild type Kv1.2 and Kv2.1 channels, but became much less potent in inhibiting Kv1.2 V370G, a mutant defective in C-type inactivation, implying that drug inhibition depends on C-type inactivation. At a high concentration (100μM), imperatorin also suppressed KATP channels.
Our results suggest that imperatorin inhibited both Kv and KATP channels.
欧前胡素是一种从白芷和蛇床子中分离出的呋喃香豆素。它具有多种神经调节作用，如抗惊厥作用、抗焦虑作用和抗伤害感受作用。尽管已有报道证明其对神经元电压门控钠通道（VGSC）和瞬时受体电位（TRP）V1通道有作用，但迄今为止尚无研究表明该化合物是否会影响电压门控钾通道（Kv）和ATP敏感性钾通道（KATP）。
我们采用全细胞模式电压钳技术研究了欧前胡素对钾通道的影响。
欧前胡素抑制分化的神经元NG108-15细胞中的Kv通道，并使稳态失活曲线向左移动，而不影响激活门控。欧前胡素还抑制异源表达的野生型Kv1.2和Kv2.1通道，但对抑制C型失活缺陷的突变体Kv1.2 V370G的效力明显降低，这意味着药物抑制作用取决于C型失活。在高浓度（100μM）下，欧前胡素也抑制KATP通道。
我们的结果表明，欧前胡素抑制Kv和KATP通道。
