Enhanced GABAA receptor-mediated activity following activation of NMDA receptors in Cajal-Retzius cells in the developing mouse neocortex
Enhanced GABAA receptor-mediated activity following activation of NMDA receptors in Cajal-Retzius cells in the developing mouse neocortex
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DOI：
10.1113/jphysiol.2003.042556
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发表时间：
2003-07-01
影响因子：
5.5
通讯作者：
Yeh, HH
中科院分区：
文献类型：
--
作者：
Chan, CH;Yeh, HH
Cajal-Retzius（CR）细胞是发育中的新皮层中最早产生的神经元群体之一，并且涉及调节皮层分层。在啮齿类动物中，CR细胞是短暂的，仅在出生后2-3周内存在。虽然先前的电生理学研究已经证明了CR细胞中存在NMDA和GABA（A）受体，但对这些受体的功能特性知之甚少。使用全细胞膜片钳技术在新皮层切片，我们证实了存在的D-氨基磷酸戊酸（APV）和艾芬普地尔敏感的NMDA受体，并发现，这种受体亚型的功能表达是应变特异性的。NMDA诱导的反应始终伴随着被APV和艾芬地尔阻断的超驰电流瞬变。此外，荷包牡丹碱很容易消除这些瞬变而不影响NMDA诱导的电流响应。这些压倒性的电流瞬变的产生依赖于细胞内Ca 2+，并通过透析与高亲和力的Ca 2+螯合剂BAPTA来防止。总体而言，本研究揭示了这些受体之间的协同相互作用，其中NMDA受体的激活通过Ca 2+依赖性机制导致GABA（A）受体介导的活性增强。
Cajal-Retzius (CR) cells are among the earliest generated population of neurons in the developing neocortex and have been implicated in regulating cortical lamination. In rodents, CR cells are transient, being present only up to 2-3 weeks after birth. Although previous electrophysiological studies have demonstrated the presence of NMDA and GABA(A) receptors in CR cells, little is known about the functional properties of these receptors. Using whole-cell patch-clamp techniques in neocortical slices, we confirmed the presence of D-aminophosphonovaleric acid (APV)- and ifenprodil-sensitive NMDA receptors, and found that the functional expression of this receptor subtype is strain specific. The NMDA-induced response was consistently accompanied by overriding current transients that were blocked by APV and ifenprodil. In addition, bicuculline readily abolished these transients without affecting the NMDA-induced current response. The generation of these overriding current transients was dependent upon intracellular Ca2+ and was prevented by dialysis with the high-affinity Ca2+-chelator BAPTA. Overall, this study uncovered a synergistic interaction between these receptors, whereby activation of NMDA receptors leads to enhanced GABA(A) receptor-mediated activity through a Ca2+-dependent mechanism.