Inhibitory effects of a bisbenzylisoquinline alkaloid dauricine on HERG potassium channels

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• 作者：Jing Zhao ; Yong Lian ; Chunfeng Lu ; Li Jing ; Haitao Yuan ; Shuangqing Peng ; ^{zhaojing106@163.com} ; ^{pengsq@hotmail.com}
• 关键词：Dauricine ; HEK293 cells ; HERG ; Patch cl Potassium channel ; APD prolongation
• 刊名：Journal of Ethnopharmacology
• 出版年：2012
• 期刊代码：26_03788741
• 类别：pha
• 出版时间：1 June, 2012
• 卷：141
• 期：2
• 页码：685-691
• 文件大小：947 K

摘要

Ethnopharmacological relevance

The roots of Menispermum dauricum have been widely used for the treatment of inflammation, allergy and arrhythmia in China for a long time. Dauricine (Dau), a bisbenzylisoquinline alkaloid from Menispermum dauricum, mainly contributes to the anti-arrhythmic effect and has received pharmacological attention. Dau can prolong the action potential duration (APD), which has been attributed to its ability to modulate Ca²⁺ and several K⁺ channels. However, its effects on human-ether-a-go-go-related gene (HERG) channels are unknown.

Aim of the study

The effects of Dau on HERG channels were investigated.

Materials and methods

Whole-cell patch-clamp technique was used to record HERG current (I_HERG) carried by recombinant HERG channels expressed in HEK293 cells.

Results

Dau inhibited I_HERG in a concentration-dependent manner with an IC₅₀ of 3.5 渭M. Development of block and washout were fast. The inhibitory action of Dau was contingent on channel gating, showing significant voltage and time dependence. Dau inhibited I_HERG in the open and inactivated states, but not in the closed states. The activation curve was shifted in a negative direction.

Conclusions

Dau inhibits HERG encoded potassium channels and this action might be a molecular mechanism for the previously reported APD prolongation with this drug.