热敏感TRPV3通道门控调节研究

项目名称： 热敏感TRPV3通道门控调节研究

项目编号： No.31271209

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 姚镜

作者单位： 武汉大学

项目金额： 88万元

中文摘要： 热敏TRPV3通道属瞬时受体势通道家族中的一员，在角化细胞、三叉神经节和大脑等组织中有大量表达。温度和一些化学性刺激均可引起通道开放。TRPV3通道具有敏化特征，通道电流在重复刺激下会在一定范围内逐渐增大。通道的门控性是离子通道最重要的基本性质之一，也是离子通道研究的核心内容。本研究拟综合应用膜片钳和分子遗传学等方法，从三方面对TRPV3通道的门控调节进行研究：（1）了解酸性pH对TRPV3通道电流的增强作用并探明H+在通道蛋白上的作用位点；（2）确定影响TRPV3通道电流敏感化过程的关键氨基酸；（3）探明BAPTA和其结构类似物以及二氧杂环己烷等化合物分子对TRPV3通道电流的调节作用，及其在通道蛋白上的作用位点。由于TRPV3通道与热感知、疼痛传导、瘙痒和毛发生长等生理、病理过程密切相关，故该课题的研究结果不仅有一定的科学理论意义，同时对疼痛、炎症等疾病的认识及药物开发也具有重要价值。

中文关键词： 离子通道；热敏TRP通道；门控调节；痛觉传导；膜片钳记录

英文摘要： Thermal TRPV3 channels is one of the transient receptor potential (TRP) superfamily, shares the common property of polymodal gating as many other TRP channels.TRPV3 channel is highly expressed in skin keratinnocytes and in a variety of neural cells, and has been implicated in pain and thermo-sensation and as well as being a molecular target of some allergens and skin sensitizers.This channel displays a unique property that repeated stimulation results in gradual increases of its activity, a process that is known as sensitization and is observed in both native cells and cell lines. The opening and closing of the channel gate, called gating, are the most fundmental property of ion channels, which can be controlled by various different means. Dysfunction of ion channels can cause a variety of diseases. Together with the methods of patch-clamp recordings and genetic mutation techniques and the structural information, we are aiming to investigate (1) how acid pH potentiates the activities of TRPV3 channels, and (2) the mechanisms and structural determinants underlying the sensitization process, and (3) to screen the regulatory compounds for effect on the activities of the channel and to identify the interaction/recognition sites between them as well. Taken together, our research aims to define pathways that control a

英文关键词： Ion channel；thermal TRP channel；gating and regualtion；pain transduction；patch-clamp recording