全麻药物受体和离子通道靶标研究是麻醉学研究领域的热点。我们前期工作利用KCNT1基因敲除的小鼠发现KCNT1钾通道在氟烷类麻醉药物和静脉麻醉药物丙泊酚的全身麻醉效应中起不同的作用。本课题以此为依据，通过行为学、形态学和电生理研究比较分析不同全麻药物在野生型小鼠、KCNT1通道基因敲除小鼠和KCNT1通道突变过度激活小鼠中的效果，揭示KCNT1通道参与不同全麻药物作用过程中神经元兴奋性、突触传递变化的异同。我们也将运用表达KCNT1通道的慢病毒核团定位注射方法来辨明KCNT1通道参与全麻的中枢核团。同时，通过分子突变和电生理实验解构 KCNT1通道的氯离子结合位点，并阐明KCNT1通道与GABAa受体、NMDA受体功能上相互作用的分子机制。综上所述，本课题结合在体和离体的方法阐释KCNT1通道在不同全麻药物作用过程中的机制，并以此深化对全身麻醉原理的理解，为发展新的全麻药物提供帮助。

Research on receptors or ion channels targets of general anesthetics is a hot field of general anesthesia studying. Our preliminary work found the KCNT1 potassium ion channel plays different roles in the process of general anesthesia induced by halothane class A narcotics and propofol. Based on this preliminary data, we will identify the role of KCNT1 channels played during the process of general anesthesia induced by different general anesthetics by comparing the effects of general anesthetics on wild type mice, KCNT1 KO mice and KCNT1 over-activity mice. We will investigate the change of neural excitability, synapse transmission induced by different general anesthetics by using behaviour, morphological and electro-physiological methods. This project also plans to address the neuronal nucleus in which KCNT1 channels play their roles by taking advantage of stereotactic injection KCNT1 KO mice with lenti-virus that carried KCNT1 channel gene. In the meantime, we will also address the Cl- binding site of KCNT1 channel by using molecular mutation and electrophysiology method. Also more experiments will be done to dissect the functional interaction of GABAa receptor and NMDA receptor with KCNT1 channels. Taken together, this project combined methods in vivo and in vitro to dissect the mechanism of KCNT1 channel that are involved in general anesthesia process induced by different general anesthetics. This project will increase our understanding of principles of general anesthesia and is helpful for developing new general anesthetics.