Repeated application of 4-aminopyridine provoke an increase in entorhinal cortex excitability and rearrange AMPA and kainate receptors.
Repeated application of 4-aminopyridine provoke an increase in entorhinal cortex excitability and rearrange AMPA and kainate receptors.
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重复使用 4-氨基吡啶会引起内嗅皮层兴奋性增加，并重新排列 AMPA 和红藻氨酸受体。
DOI：
10.1007/s12640-014-9515-7
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发表时间：
2015
影响因子：
3.7
通讯作者：
Borbély S
中科院分区：
文献类型：
--
作者：
Borbély S
内嗅皮层是一个高度容易癫痫发作的脑区。本实验观察了反复惊厥对大鼠内嗅皮层脑片上离子型谷氨酸受体(IGluRs)的影响。每日给予4-氨基吡啶(4-AP)诱发癫痫发作。通过电生理学、药理学和组织学研究，确定反复发作时iGluRs突触效能和敏感性的变化。重复4-AP致痫可增加大鼠内嗅皮层脑片诱发突触场反应的幅度。虽然特异性拮抗剂GYKI 52466对AMPA受体抑制的易感性略有降低，但对N-甲基-D-天冬氨酸受体拮抗剂APV的反应性仍未受影响。对iGluRs二价阳离子通透性的测试显示，通过非NMDA受体的钙内流减少。半定量组织印迹分析显示，GluA1-4、GluA1、GluA2、GluK5、GluN1和GluN2A亚单位蛋白表达均有不同程度的改变。GluA1-4、GluA2和GluK5受体亚基水平显著降低，GluA1和GluN2A蛋白水平适度升高。结果表明，尽管AMPA/海人藻酸受体活性降低，但每天重复10天的短暂惊厥仍可增加整体内嗅皮层的兴奋性，这可能是通过改变局部网络敏感性而实现的。
Entorhinal cortex is a highly epilepsy-prone brain region. Effects of repetitive seizures on ionotropic glutamate receptors (iGluRs) were investigated in rat entorhinal cortex slices. Seizures were induced by daily administration of 4-aminopyridine (4-AP). Electrophysiological, pharmacological and histological investigations were carried out to determine changes in synaptic efficacy and in sensitivity of iGluRs due to recurring seizures. Repeated 4-AP-induced seizures increased the amplitude of evoked synaptic field responses in rat entorhinal cortical slices. While vulnerability to inhibition of AMPA receptors by the specific antagonist GYKI 52466 was slightly reduced, responsiveness to NMDA receptor antagonist APV remained unaffected. Testing of bivalent cation permeability of iGluRs revealed reduced Ca2+-influx through non-NMDA receptors. According to the semi-quantitative histoblot analysis GluA1–4, GluA1, GluA2, GluK5, GluN1 and GluN2A subunit protein expression differently altered. While there was a marked decrease in the level of GluA1–4, GluA2 and GluK5 receptor subunits, GluA1 and GluN2A protein levels moderately increased. The results indicate that brief convulsions, repeated daily for 10 days can increase overall entorhinal cortex excitability despite a reduction in AMPA/kainate receptor activity, probably through the alteration of local network susceptibility.