Author/Authors :
Hong Liu، نويسنده , , Yang Li، نويسنده , , Mingke Song، نويسنده , , Xiaojian Tan، نويسنده , , Feng Cheng، نويسنده , , Suxin Zheng، نويسنده , , Jianhua Shen، نويسنده , , Xiaomin Luo، نويسنده , , RuYun Ji، نويسنده , , Jianmin Yue، نويسنده , , Guoyuan Hu، نويسنده , , Hualiang Jiang and Helmut Grubmüller، نويسنده , , KaiXian Chen، نويسنده ,
Abstract :
Potassium ion (K+) channels are attractive targets for rational drug design. Based upon a three-dimensional model of the eukaryotic K+ channels, the docking virtual screening approach was employed to search the China Natural Products Database. Compounds were ranked according to the relative binding energy, favorable shape complementarity, and potential of forming hydrogen bonds with the K+ channel. Four candidate compounds found by virtual screening were investigated by using the whole-cell voltage-clamp recording in rat dissociated hippocampal neurons. When applied extracellularly, compound 1 markedly depressed the delayed rectifier K+ current (IK) and fast transient K+ current (IA), whereas compounds 2, 3, and 4 exerted a more potent and selective inhibitory effect on IK. Intracellular application of the four compounds had no effect on both the K+ currents.
