Glutamate transport blockade has a differential effect on AMPA and NMDA receptor-mediated synaptic transmission in the developing barrel cortex
Glutamate transport blockade has a differential effect on AMPA and NMDA receptor-mediated synaptic transmission in the developing barrel cortex
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DOI：
10.1016/s0028-3908(99)00270-1
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发表时间：
2000-01-01
影响因子：
4.7
通讯作者：
Isaac, JTR
中科院分区：
文献类型：
--
作者：
Kidd, FL;Isaac, JTR
高亲和力谷氨酸转运在维持CNS中低细胞外谷氨酸浓度中起重要作用。由于谷氨酸转运蛋白功能丧失引起的兴奋性毒性与中风和肌萎缩侧索硬化症（ALS）等疾病过程有关。我们研究了谷氨酸转运抑制剂对丘脑皮层突触在开发（出生后第3-8天）第IV层神经元在桶皮质的丘脑皮层切片制备和全细胞记录的影响。D，L-苏型-β-羟基天冬氨酸（THA），THA和二氢红藻氨酸（DHK）的组合，或L-反式-吡咯烷-2，4-二羧酸（tPDC）的谷氨酸转运的抑制，引起AMPA和红藻氨酸受体介导的双组分兴奋性突触后电流（AMPA/KA EPSC）的可逆性阻断。环噻嗪（CTZ）没有阻断这种作用，表明这不是由于AMPAR的脱敏。在NMDA受体未被阻断的条件下，转运抑制剂引起NMDA受体的大量激活，导致记录的快速丢失。以前的研究使用这些转运抑制剂对老年动物的脑切片报告没有或只有轻微的影响突触传递。因此，本研究的数据表明，发育中的新皮层神经元对谷氨酸转运蛋白功能特别敏感。此外，转运抑制的作用取决于神经元是否充分去极化以缓解NMDA受体的电压依赖性阻滞。(C)2000爱思唯尔科技有限公司版权所有。
High affinity glutamate transport plays an important role in maintaining a low extracellular glutamate concentration in the CNS. Excitotoxicity due to a loss of glutamate transporter function has been implicated in disease processes such as stroke and amyotrophic lateral sclerosis (ALS). We studied the effects of glutamate transport inhibitors on thalamocortical synapses at developing (postnatal day 3-8) layer IV neurons in the barrel cortex using the thalamocortical slice preparation and whole-cell recordings. Inhibition of glutamate transport by D,L-threo-beta-hydroxyaspartate (THA), a combination of THA and dihydrokainate (DHK), or by L-trans-pyrrolidine-2,4-dicarboxylate (tPDC), caused a reversible blockade of AMPA and kainate receptor-mediated dual component excitatory postsynaptic currents (AMPA/KA EPSCs). This effect was not blocked by cyclothiazide (CTZ) indicating that is was not due to desensitisation of AMPARs. Under conditions in which NMDA receptors were unblocked the transport inhibitors caused the massive activation of NMDA receptors leading to the rapid loss of recordings. Previous studies using these transport inhibitors on brain slices from older animals reported no or only modest effects on synaptic transmission. Therefore the data in the present study suggest that neurons in the developing neocortex are particularly sensitive to glutamate transporter function. Furthermore the effects of transport inhibition are dependent upon whether neurons are sufficiently depolarised to relieve the voltage-dependent block of NMDA receptors. (C) 2000 Elsevier Science Ltd. All rights reserved.