TREK1钾通道是一种持续开放的背景电流，对于稳定神经元膜电位有重要作用。该通道受多种因素调控，包括膜张力、脂质分子、挥发性麻醉剂等因素。该通道可能与抗抑郁、神经保护、痛觉等多种病理过程有关。目前对于极性脂质分子和膜张力开放TREK1通道的分子机制尚不清楚。我们综合结构分析、单通道电生理和晶体结构方法从以下三个方面阐明膜张力和脂质分子调控TREK1的机制：1.针对可能的关键区域开展定点突变和单通道功能研究，检测脂质分子和膜张力开放通道的能障变化。2.通过晶体结构的研究，争取看到脂质分子与TtMscS通道的结合，同时积极开展对TREK1钾通道的表达纯化和晶体学研究。 3. 记录和分析TREK1的单通道电流，为阐明TREK1钾通道的分子机制提供新证据。本项目具有很好的研究基础，可以保证本项目能够顺利开展。本项目实施将有助于全面理解TREK1钾通道在抗抑郁、神经保护等各种生理和病理程中的作用。

Background TREK1 channels play a key role in stabilizing the resting membrane potential. They are modulated by mechanical stretch, phospholipids and transmitters, etc. TREK1 is involved in the physiology and pharmacology process of depression，neuron protection, and pain. The gating mechanism of TREK1 by membrane tension and phospholipids is still unexplored, so we combine the methods of structural analysis , single channel recording and crystallography to answer 3 important questions: 1) The role of "G-loop gate" during the process of activation of TREK1 by the stimulations of membrane stretch and phospholipids? The mutations at the area of G-loop gate and single channel recording will be performed on TREK1 channels. 2) To determine the interaction between lipids and TREK channel by the methods of crystallography. 3) single channel recording and analysis are performed to reveal the gating kinetics of TREK1 channels.We have achieved preliminary results to support that this project is running well. This projects will provide important evidence for role of TREK1 in physiology and pharmacology conditions such as antidepressant, neuroprotection, and pain, etc.