AMPA受体是离子通道型谷氨酸受体亚型之一，主要介导脑内的快速兴奋性神经传递，是神经元兴奋性突触后电流（EPSC）的物质基础，在许多神经精神系统疾病如癫痫、精神分裂症、抑郁症等的病理生理过程中发挥着关键作用。近年来，在中枢神经系统发现了多种AMPA受体辅助调节蛋白(TARPs)，这些蛋白能够在突触后膜上与AMPA受体相互作用，参与调控AMPA受体的生理学和药理学特性，因此，TARPs成为AMPA受体药物研究的新方向，但是TARPs与AMPA受体相互作用的分子机制目前还不清楚，基于申请者以往的对AMPA受体和TARPs的研究基础，本课题拟通过质谱和电生理学技术，揭示AMPA受体和TARPs的相互作用位点，着力阐明TARPs调控AMPA受体开放与关闭的分子机制，为研发AMPA受体调节药物提供理论依据。

AMPA receptor is one of glutamate glutamate-gated ion channels that mediate fast excitatory synaptic transmission in the mammalian CNS. It plays a major role in EPSC and related with many central nerves disorder such as epilepsy, depression and schizophrenia. In recently, there are many kinds of transmembrane AMPA receptor regulatory proteins (TARPs) found in CNS, which could regulate the physiological and pharmacological function of AMPA receptor. The discovery of TARPs points a new pathway to design AMPA receptor modulator. However, the precise mechanism of AMPA receptor/TARPs interaction is poorly understood. Here we will analyze the relative binding site of AMPA receptor and TARPs by electrophysiology and mass spectrometry to further clarify the mechanism of AMPA receptor opening and desensitization and provide a target for AMPA receptor drug design.