大电导钙激活钾通道（BKCa）是血管平滑肌细胞膜上的主要离子通道，在血管舒缩功能调控中起重要作用。BKCa通道蛋白在内质网合成、高尔基体加工后，需经过一系列复杂机制转运并组装到质膜上，才能发挥生理功能。小G蛋白家族成员Rab在质膜内侧及多种胞内囊泡结构中存在，具有调节细胞信号转导、囊泡转运和离子通道活动等功能。本项目是在我们前期研究提示Rab参与BKCa通道蛋白质膜转运的工作基础上，拟采用荧光共振能量转移、共聚焦显微成像、流式细胞术、电生理（膜片钳）和胶体金免疫电镜等多种技术，以Rab为点、BKCa通道蛋白转运的三个主要过程为线，研究Rab在一些辅助因子（磷脂酰肌醇等）的帮助下，对BKCa通道蛋白内质网-高尔基体-质膜转运及细胞膜循环（内吞和再循环插入到细胞膜）时空特性的调控作用及机制。该研究对于阐明BKCa通道蛋白细胞膜转运机制和血管平滑肌的功能调控有着重要理论意义。

Large conductance calcium-activated potassium channels (BKCa) are broadly expressed in vascular smooth muscle cells (SMCs) and play a crucial role in regulating the vascular tone. After being synthesized and processed in endoplasmic reticulum and golgi apparatus respectively, BKCa protein should be transported to the plasmic membrane to take physiological function with complicated mechanisms. As one member of the small GTPase family, Rab expresses extensively in the intracellular membrane and subcellular compartments with the role of regulating signal transduction, vesicle transportation and ion channel's activity. Taken previous research which demonstrating that Rab participated in the trafficking of BKCa, we propose to further investigate the mechanism that Rab,together with some cofactors, regulates BKCa through the pathway of endoplasmic reticulum to golgi apparatus and plasma membrane as well as cycling in the membrane(endocytosis and recycling into the membrane). To confirm this hypothesis, multiple biological methods will be used including FRET, confocal, flow cytometry, electrophysiology and immunoelectron microscopy labelled with gold. These researches aim to reveal the membrane trafficking mechanism of BKCa and it will be of great value for the regulation of vascular smooth muscle.