延迟整流外向钾通道（IK）由Kv2.1和Kv2.2亚单位组成。自1992年首次报道以来的大量研究表明，PKA通过磷酸化修饰Kv.2.1调控通道的电压门控特性和膜上的活动，且有重要意义。由于PKA不修饰Kv2.2，有关Kv2.2的调控研究遭受瓶颈。我们近期研究发现，Kv2.2在皮层神经元IK中占据重要地位，可被抗抑郁症药物抑制；前期的预初实验显示，激活PKC可改变Kv2.2的电流幅度和通道电压门控特性，说明存在着与Kv2.1不同的、PKC介导的磷酸化调控机制，与PKA调控Kv2.1的途径完全不同，但国内外尚无相关报道。本课题将用转染Kv.2.2的细胞株、皮层脑片和培养神经元，结合膜片钳记录、分子生物学和免疫组化等研究方法，系统探讨PKC介导的Kv2.2调控机制、该调控对通道电压门控特性和膜上活动的影响，以及调控的生物学意义。为深入研究Kv2.2离子通道的结构与功能、调控与生理作用提供平台。

Mammalian voltage-gated delayed rectifier outward potassium channel (IK) is mainly composed by Kv2.1 and Kv2.2 alpha-subunit. Since the first reported in 1992, the study on Kv2.1 for its regulation mechanisms by PKA and biological significance was in-depth and detail. Because PKA does not modify Kv2.2, regulation of Kv2.2 suffered a bottleneck. that Kv2.2 is main component in cortical neurons IK, and can be antidepressants suppression; the preliminary experiments show that the activation of PKC significantly modified Kv2.2 amplitude and voltage-gated characteristics, suggesting a completely different mechanism with Kv2.1 and PKC-mediated phospholation will be involved. However, no related report was found so far. This project will use the model of HEK-293 cells transfected Kv.2.2, cultured and acutely isolated cortical slices and neuron, combining techniques with current and voltage patch clamp recording, molecular biology, and immunohistochemistry, to explore (1) the mechanism of PKC-mediated regulation of Kv2.2; (2) the function of PKC-mediated modulation on voltage-gated characteristics and post-translational behavioral of Kv2.2, and (3) role in neuronal excitability and survival with PKC-mediated Kv2.2 regulation. Our study will provide a research platform for Kv2.2 study in in-depth and detail.