来自人类海马体致痫灶的星形胶质细胞表现出类似动作电位的反应。

Astrocytes from human hippocampal epileptogenic foci exhibit action potential-like responses.

作者信息

O'Connor E R, Sontheimer H, Spencer D D, de Lanerolle N C

机构信息

Department of Neurosurgery, Yale University School of Medicine, New Haven, Connecticut 06520-8082, USA.

出版信息

Epilepsia. 1998 Apr;39(4):347-54. doi: 10.1111/j.1528-1157.1998.tb01386.x.

DOI:10.1111/j.1528-1157.1998.tb01386.x

PMID:9578024

Abstract

PURPOSE

We studied Na+ channel expression and the ability to generate action potential (AP)-like responses in primary cultures of human astrocytes by whole cell patch-clamp recording techniques.

METHODS

Tissue samples from 22 patients with various classifications of temporal lobe epilepsy (TLE) were plated to form separate astrocyte cultures from three regions; the hippocampus, parahippocampus, and anterolateral temporal neocortex.

RESULTS

The resting membrane potential of seizure focus astrocytes (MTLE, mesial TLE) was significantly depolarized (approximately -55 mV) as compared with cortical astrocytes (-80 mV). Hippocampal astrocytes from other substrates for TLE (MaTLE, mass-associated TLE; PTLE, paradoxical TLE) in which the hippocampus is not the seizure focus displayed resting membrane potentials similar to those of neocortical astrocytes (approximately -75 mV). Astrocytes from the seizure focus (MTLE) displayed much larger tetrodotoxin (TTX)-sensitive Na+ currents with -66-fold higher Na+ channel density (113.5 +/- 17.41 pA/pf) than that of comparison neocortical astrocytes (1.7 +/- 3.7 pA/pf) or than that of the hippocampal and parahippocampal astrocytes of the MaTLE and PTLE groups. As a consequence of this higher channel density, seizure focus astrocytes were capable of generating AP-like responses. However, at the resting potential, most Na+ channels are inactive and no spontaneous firing was observed. In contrast, astrocytes in the comparison neocortex from all groups and the hippocampus and parahippocampus from the MaTLE and PTLE groups could not fire AP-like responses even after large current injections.

CONCLUSIONS

The function of Na+ channels in these astrocytes is unclear. However, the marked differences in seizure focus astrocytes as compared with cortical and nonseizure focus hippocampal astrocytes suggest a more active role for astrocytes associated with hyperexcitable neurons at a seizures focus.

摘要

目的

我们运用全细胞膜片钳记录技术，研究了原代培养的人星形胶质细胞中钠离子通道的表达情况以及产生类动作电位（AP）反应的能力。

方法

从22例不同类型颞叶癫痫（TLE）患者身上获取组织样本，分别从海马体、海马旁回和颞叶新皮质前外侧三个区域培养星形胶质细胞。

结果

与皮质星形胶质细胞（-80 mV）相比，癫痫病灶星形胶质细胞（内侧颞叶癫痫，MTLE）的静息膜电位显著去极化（约-55 mV）。其他颞叶癫痫发病部位（伴有肿块的颞叶癫痫，MaTLE；矛盾性颞叶癫痫，PTLE）的海马星形胶质细胞，其海马体并非癫痫病灶，其静息膜电位与新皮质星形胶质细胞相似（约-75 mV）。癫痫病灶（MTLE）的星形胶质细胞表现出更大的河豚毒素（TTX）敏感型钠离子电流，其钠离子通道密度比对照新皮质星形胶质细胞（1.7±3.7 pA/pf）或MaTLE和PTLE组的海马及海马旁回星形胶质细胞高66倍（113.5±17.41 pA/pf）。由于这种更高的通道密度，癫痫病灶星形胶质细胞能够产生类动作电位反应。然而，在静息电位时，大多数钠离子通道处于失活状态，未观察到自发放电。相比之下，所有组的对照新皮质中的星形胶质细胞以及MaTLE和PTLE组的海马体和海马旁回中的星形胶质细胞，即使在大电流注入后也无法产生类动作电位反应。