Wu Long-Jun, Vadakkan Kunjumon I, Zhuo Min
Department of Physiology, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada.
Glia. 2007 Jun;55(8):810-21. doi: 10.1002/glia.20500.
Microglial cells are the resident macrophages that are involved in brain injuries and infections. Recent studies using transcranial two-photon microscopy have shown that ATP and P2Y receptors mediated rapid chemotactic responses of miroglia to local injury. However, the molecular mechanism for microglial chemotaxis toward ATP is still unknown. To address this question, we employed a combination of simultaneous perforated whole-cell recordings and time-lapse confocal imaging in GFP-labeled microglia in acute brain slices from adult mice. We found that ATP-induced rapid chemotaxis is correlated with P2Y receptor associated-outward potassium current in microglia. Activation of both P2Y receptor and its associated potassium channels are required for ATP-induced chemotaxis and baseline motility of microglial cells. The chemotaxis required the activation of phosphoinositide 3-kinase but not mitogen-activated protein kinase pathway. Our results provide strong evidence that P2Y receptor-associated outward potassium channels and the phosphoinositide 3-kinase pathway are important for ATP-induced microglial motility in acute brain slices.
小胶质细胞是参与脑损伤和感染的常驻巨噬细胞。最近使用经颅双光子显微镜的研究表明，ATP和P2Y受体介导小胶质细胞对局部损伤的快速趋化反应。然而，小胶质细胞向ATP趋化的分子机制仍然未知。为了解决这个问题，我们在成年小鼠急性脑切片中对绿色荧光蛋白标记的小胶质细胞同时采用穿孔全细胞记录和延时共聚焦成像技术。我们发现，ATP诱导的快速趋化与小胶质细胞中P2Y受体相关的外向钾电流相关。ATP诱导的小胶质细胞趋化和基础运动性需要P2Y受体及其相关钾通道的激活。趋化作用需要磷酸肌醇3激酶的激活，但不需要丝裂原活化蛋白激酶途径。我们的结果提供了强有力的证据，表明P2Y受体相关的外向钾通道和磷酸肌醇3激酶途径对急性脑切片中ATP诱导的小胶质细胞运动很重要。
