Loss of perivascular Kir4.1 potassium channels in the sclerotic hippocampus of patients with mesial temporal lobe epilepsy.
Loss of perivascular Kir4.1 potassium channels in the sclerotic hippocampus of patients with mesial temporal lobe epilepsy.
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DOI：
10.1097/nen.0b013e318267b5af
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发表时间：
2012-09
影响因子：
3.2
通讯作者：
de Lanerolle NC
中科院分区：
文献类型：
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作者：
Heuser K;Eid T;Lauritzen F;Thoren AE;Vindedal GF;Taubøll E;Gjerstad L;Spencer DD;Ottersen OP;Nagelhus EA;de Lanerolle NC
最近在小鼠中的实验数据表明，内向整流K+通道Kir4.1介导海马中的K+空间缓冲。在这里，我们用免疫组织化学方法检测Kir4.1在药物难治性颞叶癫痫患者大脑中的分布。在编码Kir4.1的基因的神经胶质条件性缺失的小鼠中证实了抗体的选择性。这些小鼠显示出标记细胞的完全丧失，表明Kir4.1仅限于神经胶质。在人类的情况下，Kir4.1免疫反应性观察到的细胞形态一致的星形胶质细胞显着减少12例海马硬化与11例无硬化和4例正常尸检对照。星形胶质细胞Kir4.1免疫反应性的丧失在血管周围最明显，仅限于胶质细胞区域。Kir4.1表达的缺失与肌营养不良蛋白和α-突触营养蛋白的缺失相关，但与β-肌营养不良蛋白聚糖的缺失无关，表明肌营养不良蛋白相关蛋白复合物的部分破坏。在海马硬化患者中发现的变化可能干扰K+稳态，并可能导致海马硬化的致癫痫性。
Recent experimental data in mice have shown that the inwardly rectifying K+ channel Kir4.1 mediates K+ spatial buffering in the hippocampus. Here we used immunohistochemistry to examine the distribution of Kir4.1 in hippocampi from patients with medication refractory temporal lobe epilepsy. The selectivity of the antibody was confirmed in mice with a glial conditional deletion of the gene encoding Kir4.1. These mice showed a complete loss of labeled cells, indicating that Kir4.1 is restricted to glia. In the human cases, Kir4.1 immunoreactivity observed in cells morphological consistent with astrocytes was significantly reduced in 12 patients with hippocampal sclerosis vs. 11 patients without sclerosis and 4 normal autopsy controls. Loss of astrocytic Kir4.1 immunoreactivity was most pronounced around vessels and was restricted to gliotic areas. Loss of Kir4.1 expression was associated with loss of dystrophin and α-syntrophin, but not with loss of β-dystroglycan, suggesting partial disruption of the dystrophin-associated protein complex. The changes identified in patients with hippocampal sclerosis likely interfere with K+ homeostasis and may contribute to the epileptogenicity of the sclerotic hippocampus.