Astrocytes in the hippocampus of patients with temporal lobe epilepsy display changes in potassium conductances
Astrocytes in the hippocampus of patients with temporal lobe epilepsy display changes in potassium conductances
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DOI：
10.1046/j.1460-9568.2000.00104.x
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发表时间：
2000-06-01
影响因子：
3.4
通讯作者：
Steinhäuser, C
中科院分区：
文献类型：
--
作者：
Hinterkeuser, S;Schröder, W;Steinhäuser, C
应用膜片钳技术研究了急性海马脑片星形胶质细胞的功能特性。在具有显著神经元细胞损失（即阿蒙角硬化）的患者中，神经胶质电流模式类似于鼠或大鼠海马中未成熟星形胶质细胞的特性。去极化电压阶跃激活延迟整流和瞬时K+电流以及河豚毒素敏感的Na+电流在所有星形胶质细胞中分析的scarpus人体组织。超极化电压引起内向整流电流，在膜电位负至-130 mV时失活。比较记录进行星形胶质细胞与病变相关的TLE患者，缺乏显着的海马组织病理学改变。这些细胞表现出较强的内向整流。为了获得定量测量，计算电流密度，并确定内向与外向K+电导的比率。在啮齿类动物脑的正常发育过程中，星形胶质细胞的内向整流逐渐增加。因此，似乎合理的建议，星形胶质细胞在人类皮肤组织返回到一个不成熟的电流模式。减少星形胶质细胞向内整流结合电刺激诱导的细胞外空间收缩可能导致受损的空间K+缓冲。这将导致神经胶质细胞和神经元响应于活性依赖性K+释放的更强和更长的去极化，因此可能有助于在人类TLE的这种特定条件下癫痫发作的产生。
Functional properties of astrocytes were investigated with the patch-clamp technique in acute hippocampal brain slices obtained from surgical specimens of patients suffering from pharmaco-resistant temporal robe epilepsy (TLE). in patients with significant neuronal cell loss, i.e. Ammon's horn sclerosis, the glial current patterns resembled properties characteristic of immature astrocytes in the murine or rat hippocampus. Depolarizing voltage steps activated delayed rectifier and transient K+ currents as well as tetrodotoxin-sensitive Na+ currents in all astrocytes analysed in the sclerotic human tissue. Hyperpolarizing voltages elicited inward rectifier currents that inactivated at membrane potentials negative to -130 mV. Comparative recordings were performed in astrocytes from patients with lesion-associated TLE that lacked significant histopathological hippocampal alterations. These cells displayed stronger inward rectification. To obtain a quantitative measure, current densities were calculated and the ratio of inward to outward K+ conductances was determined. Both values were significantly smaller in astrocytes from the sclerotic group compared with lesion-associated TLE.During normal development of rodent brain, astroglial inward rectification gradually increases. It thus appears reasonable to suggest that astrocytes in human sclerotic tissue return to an immature current pattern. Reduced astroglial inward rectification in conjunction with seizure-induced shrinkage of the extracellular space may lead to impaired spatial K+ buffering. This will result in stronger and prolonged depolarization of glial cells and neurons in response to activity-dependent K+ release, and may thus contribute to seizure generation in this particular condition of human TLE.