Properties of human glial cells associated with epileptic seizure foci
Properties of human glial cells associated with epileptic seizure foci
复制标题
DOI：
10.1016/s0920-1211(98)00059-x
复制
发表时间：
1998-09-01
影响因子：
2.2
通讯作者：
Sontheimer, H
中科院分区：
文献类型：
--
作者：
Bordey, A;Sontheimer, H
我们使用全细胞膜片钳记录，研究了来自顽固性近颞叶癫痫手术患者的急性活检切片的神经胶质细胞的生理特性。记录期间细胞充满荧光黄 (LY)，以进行形态学重建和免疫组织化学细胞识别。癫痫相关的星形胶质细胞具有复杂的、树状的、高度分支的突起，赋予它们星状外观，并且细胞对中间丝 GFAP 进行了强烈染色，正如之前报道的“反应性”星形胶质细胞。癫痫活检中的 GFAP 阳性星形胶质细胞一致表达电压激活、TTX 敏感的 Na+ 通道，显示出快速激活和失活动力学。与源自与癫痫病灶无关的组织的比较星形胶质细胞不同，这些星形胶质细胞表达的 Na+ 通道的密度足以在当前的钳夹研究中产生慢动作电位（尖峰）。在这些细胞中，Na+ 与 K+ 电导率的比率始终比人类或对照大鼠星形胶质细胞高 3-4 倍。来自癫痫患者的 17 个星形胶质细胞中的 4 个与对照大鼠海马中的 14/14 以及对照人体组织中的 5 个星形胶质细胞中的 4 个显示出缺乏内向整流 K+ 电流，而在正常星形胶质细胞中，该电流与细胞外 K+ 水平的控制有关。这些结果表明，癫痫病灶周围的星形胶质细胞在形态和生理特性上存在差异，并且癫痫病灶处的胶质细胞 K+ 缓冲可能受到损害，从而导致癫痫发作的病理生理学。 (C) 1998 Elsevier Science B.V. 保留所有权利。
We studied physiological properties of glial cells from acute slices of biopsies from patients operated for intractable mesio-temporal lobe epilepsy using whole-cell patch-clamp recordings. Cells were filled with Lucifer Yellow (LY) during recordings to allow morphological reconstruction and immunohistochemical cell identification. Seizure-associated astrocytes had complex, arborized, highly branched processes giving them a stellate appearance, and cells stained intensely for the intermediate filament GFAP as previously reported for 'reactive' astrocytes. GFAP-positive astrocytes from epilepsy biopsies consistently expressed voltage-activated, TTX-sensitive Na+ channels that showed fast activation and inactivation kinetics. Unlike comparison astrocytes, derived from tissues that were not associated with seizure foci, these astrocytes expressed Na+ channels at densities sufficient to generate slow action potentials (spikes) in current clamp studies. In these cells, the ratio of Na+ to K+ conductance was consistently 3-4-fold higher than in comparison human or control rat astrocytes. Four of 17 astrocytes from epilepsy patients versus 14/14 from control rat hippocampus and four of five in comparison human tissue showed a lack of inwardly rectifying K+ currents, which in normal astrocytes are implicated in the control of extracellular K+ levels. These results suggest that astrocytes surrounding seizure foci differ in morphological and physiological properties, and that glial K+ buffering could be impaired at the seizure focus, thus contributing to the pathophysiology of seizures. (C) 1998 Elsevier Science B.V. All rights reserved.