ENaC/DEG超家族是20世纪90年代发现的一类与多种疾病发生紧密相关的钠离子选择性离子通道，其亚家族成员ASIC和ENaC作为一些重要疾病的治疗靶点已逐步成为人们研究的热点，因此对ENaC/DEG超家族激活机制进行研究将有助于ASICs和ENaC相关疾病新药的设计和发现。本项目将在诠释外源配体激活各自对应ENaC/DEG超家族重要成员的分子基础上，对ASIC的小分子配体GMQ直接激活FaNaC，FaNaC配体FMRFamide调节ASIC3的分子基础以及ENaC小分子配体S3969调节ASIC和FaNaC的分子基础进行研究，剖析ENaC/DEG超家族重要成员小分子配体交互激活和调节机制，找出ENaC/DEG离子通道超家族重要成员之间配体激活的共性、特性，并据此进行全新分子设计与功能研究，找出新型配体，甚至是内源性配体，这对于进行ENaC/DEG家族相关重要疾病的探讨提供重要线索和前提。

The epithelial sodium channel/degenerin (ENaC/DEG) superfamily, which was cloned in the early 1990s, is a sodium-selective ion channels. These ion channels are implicated in many physiological and pathological functions. In the past years, considerable efforts have been made to develop drugs targeting those receptors. The activation mechanism of ENaC/DEG superfamily of ion channels is thus of important and will open therapeutic avenues for the diseases targeting the members of this superfamily. Here, we mainly focus on the following aspects: the structure-activity relationship of exogenous ligands and correlated important members of the ENaC/DEG super family; the activation mechanism of FaNaC by non-proton small molecule activator of ASIC channels, GMQ; the regulation mechanism of ASIC by FaNaC activator FMRFamide; the regulation mechanism of ASIC and FaNaC by S3969, the small molecule activator of ENaC, which would provide insights into the common and unique features in ligand-recognition of DEG/ENaC superfamily of ion channels. This study will allow new chemicals discovery, including the discovery of endogenous ligands，which provides clues for new function identification of this superfamily of ion channels.