Olsen Michelle L, Khakh Baljit S, Skatchkov Serguei N, Zhou Min, Lee C Justin, Rouach Nathalie
Department of Cell, Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, Alabama 35294,
Department of Physiology and Neurobiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095.
J Neurosci. 2015 Oct 14;35(41):13827-35. doi: 10.1523/JNEUROSCI.2603-15.2015.
Initial biophysical studies on glial cells nearly 50 years ago identified these cells as being electrically silent. These first studies also demonstrated a large K(+) conductance, which led to the notion that glia may regulate extracellular K(+) levels homeostatically. This view has now gained critical support from the study of multiple disease models discussed herein. Dysfunction of a major astrocyte K(+) channel, Kir4.1, appears as an early pathological event underlying neuronal phenotypes in several neurodevelopmental and neurodegenerative diseases. An expanding list of other astrocyte ion channels, including the calcium-activated ion channel BEST-1, hemichannels, and two-pore domain K(+) channels, all contribute to astrocyte biology and CNS function and underpin new forms of crosstalk between neurons and glia. Once considered merely the glue that holds the brain together, it is now increasingly recognized that astrocytes contribute in several fundamental ways to neuronal function. Emerging new insights and future perspectives of this active research area are highlighted within.
The critical role of astrocyte potassium channels in CNS homeostasis has been reemphasized by recent studies conducted in animal disease models. Emerging evidence also supports the signaling role mediated by astrocyte ion channels such as BEST1, hemichannels, and two-pore channels, which enable astrocytes to interact with neurons and regulate synaptic transmission and plasticity. This minisymposium highlights recent developments and future perspectives of these research areas.
近50年前对神经胶质细胞的初步生物物理学研究将这些细胞鉴定为电沉默细胞。这些最初的研究还证明了一种大的钾离子电导，这导致了神经胶质细胞可能通过稳态调节细胞外钾离子水平的观点。本文所讨论的多种疾病模型的研究现已为这一观点提供了关键支持。主要星形胶质细胞钾离子通道Kir4.1的功能障碍，在几种神经发育和神经退行性疾病中，似乎是神经元表型背后的早期病理事件。包括钙激活离子通道BEST-1、半通道和双孔结构域钾离子通道在内的其他星形胶质细胞离子通道的种类不断增加，它们都对星形胶质细胞生物学和中枢神经系统功能有贡献，并构成神经元与神经胶质细胞之间新的串扰形式。星形胶质细胞曾经仅仅被认为是将大脑维系在一起的胶水，现在人们越来越认识到它在几个基本方面对神经元功能有贡献。本文突出了这一活跃研究领域新出现的见解和未来展望。
动物疾病模型的最新研究再次强调了星形胶质细胞钾离子通道在中枢神经系统稳态中的关键作用。新出现的证据还支持由星形胶质细胞离子通道（如BEST1、半通道和双孔通道）介导的信号传导作用，这些通道使星形胶质细胞能够与神经元相互作用并调节突触传递和可塑性。本次小型研讨会突出了这些研究领域的最新进展和未来展望。
