The changes of potassium currents in RCS rat Müller cell during retinal degeneration
The changes of potassium currents in RCS rat Müller cell during retinal degeneration
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DOI：
10.1016/j.brainres.2011.10.011
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发表时间：
2012-01
期刊：
影响因子：
2.9
通讯作者：
Tongtao Zhao;Y. Li;Chuanhuang Weng;Zhengqin Yin
中科院分区：
文献类型：
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作者：
Tongtao Zhao;Y. Li;Chuanhuang Weng;Zhengqin Yin
膜状上皮细胞是表达膜结合钾通道的主要胶质细胞，主要介导视网膜神经元活动产生的细胞外K+的稳态调节。众所周知，网膜<s:1> ller细胞在许多病理状态下都可以被激活，但对于视网膜色素变性进展过程中网膜<s:1> ller细胞钾电流的变化却知之甚少。本研究采用英国皇家外科学院大鼠（RCS大鼠）分别采用免疫组织化学、RT-PCR、western blot和全细胞膜片钳夹技术，研究视网膜变性过程中m<s:1> ller细胞Kir4.1表达、膜特性和K+通道电流等表型和功能变化。RCS大鼠视网膜中谷氨酰胺合成酶（GS） mRNA水平在P30和P60时升高，随后逐渐下降。形态学上，p60后心肌细胞显著肥大、增殖。中间丝、胶质纤维酸性蛋白（GFAP）和波形蛋白的表达从P30开始增加，在p60达到峰值。Kir4.1通道在P30出现表达高峰。同时，m<s:1> ller细胞的K+电流在P30时显著升高，在P90时显著降低。我们认为RCS大鼠的视网膜<s:1> ller细胞在p60前发生视网膜变性而激活，然后发生明显的反应性胶质增生，导致基本膜特性发生明显变化，导致网膜<s:1> ller细胞的Kir4.1通道发生明显的功能转移，甚至失去正常的电生理特性。这一过程加重了由最初的光感受器变性引起的损伤。
Müller cells are the principal glial cells expressing membrane-bound potassium channel and predominantly mediating the homeostatic regulation of extracellular K+produced by neuronal activity in retina. It's well known that Müller cells can be activated in many pathological conditions, but little is known about the change of potassium currents of Müller cells during the progression of retinitis pigmentosa. Herein, the Royal College of Surgeons rats (RCS rat) were employed to investigate some phenotypic and functional changes of Müller cells during retinal degeneration such as the expression of Kir4.1, membrane properties and K+channel currents by using immunohistochemistry, RT-PCR, western blot and whole-cell patch clamping respectively. Compared with Müller cells in control retina, increased glutamine synthetase (GS) mRNA levels were seen at P30 and P60, and then decreased gradually in RCS rat retina. Morphologically, Müller cells showed significant hypertrophy and proliferation after p60. The increased expression of intermediate filament, glial fibrillary acidic protein (GFAP) and vimentin began at P30 and reached a peak at p60. Kir4.1 channels presented a peak expression at P30. Concomitantly, K+currents of Müller cells increased at P30 and decreased at P90 significantly. We concluded that retinal Müller cells of RCS rats underwent an activation initiated by the onset of retinal degeneration before p60 and then an obvious reactive gliosis, which led the basic membrane properties to suffer marked changes, and caused the Kir4.1 channels of Müller cells to occur a clear functional shift, even lose their normal electrophysiological properties. This process aggravates the impairment caused by the initial photoreceptor degeneration.