Unitat de Fisiologia, Departament de Ciències Fisiològiques, Genes Disease and Therapy Program IDIBELL-Institute of Neurosciences, Universitat de Barcelona, L'Hospitalet de Llobregat, 08907 Barcelona, Spain.
Centro de Investigación en red de enfermedades raras (CIBERER), ISCIII, 08907 Barcelona, Spain.
Int J Mol Sci. 2019 Feb 27;20(5):1034. doi: 10.3390/ijms20051034.
Astrocytes are the most abundant cell type in the CNS (central nervous system). They exert multiple functions during development and in the adult CNS that are essential for brain homeostasis. Both cation and anion channel activities have been identified in astrocytes and it is believed that they play key roles in astrocyte function. Whereas the proteins and the physiological roles assigned to cation channels are becoming very clear, the study of astrocytic chloride channels is in its early stages. In recent years, we have moved from the identification of chloride channel activities present in astrocyte primary culture to the identification of the proteins involved in these activities, the determination of their 3D structure and attempts to gain insights about their physiological role. Here, we review the recent findings related to the main chloride channels identified in astrocytes: the voltage-dependent ClC-2, the calcium-activated bestrophin, the volume-activated VRAC (volume-regulated anion channel) and the stress-activated Maxi-Cl. We discuss key aspects of channel biophysics and structure with a focus on their role in glial physiology and human disease.
星形胶质细胞是中枢神经系统（CNS）中最丰富的细胞类型。它们在发育过程中和成年 CNS 中发挥多种功能，对大脑内环境稳定至关重要。在星形胶质细胞中已经鉴定出阳离子和阴离子通道活性，并且认为它们在星形胶质细胞功能中发挥关键作用。尽管阳离子通道的蛋白质和生理作用变得非常清楚，但对星形胶质氯离子通道的研究还处于早期阶段。近年来，我们已经从鉴定星形胶质细胞原代培养中存在的氯离子通道活性，发展到鉴定参与这些活性的蛋白质，确定它们的三维结构，并试图深入了解它们的生理作用。在这里，我们回顾了与星形胶质细胞中鉴定出的主要氯离子通道相关的最新发现：电压依赖性 ClC-2、钙激活的 bestrophin、体积激活的 VRAC（体积调节阴离子通道）和应激激活的 Maxi-Cl。我们讨论了通道生物物理学和结构的关键方面，重点是它们在神经胶质生理学和人类疾病中的作用。
