ATP敏感性钾通道（ATP-sensitive potassium channels，K-ATP通道）是机体内偶联细胞能量代谢和电活动的独特生物感受器。申请者前期发现Kir6.2亚基构成的K-ATP通道敲除对MPTP联合丙磺舒所致帕金森病（PD）模型小鼠中脑黑质致密部（SNc）多巴胺（DA）能神经元具有保护作用，但是Kir6.2/K-ATP通道的保护作用机制至今不清楚。本项目拟在前期工作基础上，应用已制备的Kir6.2敲除小鼠，在整体、细胞和分子水平系统研究Kir6.2/K-ATP通道对中脑SNc区DA神经元的调节作用及其与PD发生的相关性，阐明Kir6.2/K-ATP通道敲除对中脑SNc区DA神经元保护作用的细胞与分子机制，为PD临床治疗提供有益的思路，也为发展基于Kir6.2/K-ATP通道的神经保护剂提供新靶标。

ATP-sensitive potassium channels (K-ATP channels) are unique biological receptors linking between cellular energetic and electrical excitability. We recently found that genetic inactivation of Kir6.2-containing K-ATP channels (Kir6.2/K-ATP channels) resulted in a protection of substantia nigra pars compacta (SNc) dopaminergic (DA) neurons in the chronic MPTP and probenecid (MPTP/p) mouse model of Parkinson's disease, while the mechanism is still unclear. Therefore, based on the previous work, the aim of present studies is to investigate the role of Kir6.2/K-ATP channels on DA midbrain neurons in SNc, and the correlation with PD by using Kir6.2/K-ATP channels knockout mice in vivo and in vitro, then clarify the cellular and molecular mechanisms that Kir6.2/K-ATP channels knockout protects the degeneration of SNc DA neurons in midbrain. This study has provided useful ideas for clinical treatment of PD and raised a new target for the development of neuroprotective agents based on Kir6.2/K-ATP channels.