A potassium channel-linked mechanism of glial cell swelling in the postischemic retina
A potassium channel-linked mechanism of glial cell swelling in the postischemic retina
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DOI：
10.1016/j.mcn.2004.04.005
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发表时间：
2004-08-01
影响因子：
3.5
通讯作者：
Bringmann, A
中科院分区：
文献类型：
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作者：
Pannicke, T;Iandiev, I;Bringmann, A
神经胶质细胞肿胀是脑和视网膜水肿形成的主要原因，其细胞机制尚不清楚。在这里，我们表明，胶质细胞在缺血后大鼠视网膜，而不是在控制视网膜，肿胀后低渗应力。对照细胞的肿胀可以诱发时，其K+通道被阻断。短暂缺血后，胶质细胞强烈下调其K+电导和其突出的Kir4.1蛋白在血管和玻璃体的表达。与此相反，水通道蛋白-4（AQP 4）（水通道）蛋白的表达在缺血后仅略有改变。D-2多巴胺能受体的激活防止低渗神经胶质细胞肿胀。本研究结果阐明了耦合的跨膜水通量的K+电流在神经胶质细胞，并揭示了改变的K+通道表达的细胞毒性水肿的发展中的作用。我们提出了一种机制，缺血后的神经胶质细胞肿胀，其K+电导的下调，防止细胞内积累的K+离子的排放，从而导致血液通过水通道蛋白进入神经胶质细胞的水通量驱动。抑制这些水通量可能有利于防止缺血诱发的神经胶质细胞肿胀。(C)2004年爱思唯尔公司All rights reserved.
The cellular mechanisms underlying glial cell swelling, a central cause of edema formation in the brain and retina, are not yet known. Here, we show that glial cells in the postischemic rat retina, but not in control retina, swell upon hypotonic stress. Swelling of control cells could be evoked when their K+ channels were blocked. After transient ischemia, glial cells strongly downregulated their K+ conductance and their prominent Kir4.1 protein expression at blood vessels and the vitreous body. In contrast, the expression of the aquaporin-4 (AQP4) (water channel) protein was only slightly altered after ischemia. Activation of D-2 dopaminergic receptors prevents the hypotonic glial cell swelling. The present results elucidate the coupling of transmembraneous water fluxes to K+ currents in glial cells and reveal the role of altered K+ channel expression in the development of cytotoxic edema. We propose a mechanism of postischemic glial cell swelling where a downregulation of their K+ conductance prevents the emission of intracellularly accumulated K+ ions, resulting in osmotically driven water fluxes from the blood into the glial cells via aquaporins. Inhibition of these water fluxes may be beneficial to prevent ischemia-evoked glial cell swelling. (C) 2004 Elsevier Inc. All rights reserved.