HETEROMERIC NMDA RECEPTORS - MOLECULAR AND FUNCTIONAL DISTINCTION OF SUBTYPES
HETEROMERIC NMDA RECEPTORS - MOLECULAR AND FUNCTIONAL DISTINCTION OF SUBTYPES
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DOI：
10.1126/science.256.5060.1217
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发表时间：
1992-05-22
期刊：
影响因子：
56.9
通讯作者：
SEEBURG, PH
中科院分区：
文献类型：
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作者：
MONYER, H;SPRENGEL, R;SEEBURG, PH
谷氨酸门控离子通道的N-甲基-D-天冬氨酸（NMDA）受体亚型具有高钙渗透性和独特的电压依赖性镁敏感性，并受甘氨酸调节。分子克隆鉴定了大鼠脑中编码NMDA受体亚单位NMDAR 2A（NR 2A）、NR 2B和NR 2C的三种互补DNA，它们在序列上有55%至70%的相同性。它们在结构上相关，与其他兴奋性氨基酸受体亚基（包括NMDA受体亚基NMDAR 1（NR 1））的序列同一性小于20%。在培养的细胞中表达后，新的亚基产生突出的，典型的谷氨酸和NMDA激活的电流，只有当他们在异聚体配置与NR 1。NR 1-NR 2A和NR 1-NR 2C通道的门控行为和镁敏感性不同。这种异聚体NMDA受体亚型可能存在于神经元中，因为NR 1信使RNA在整个成熟大鼠脑中合成，而NR 2信使RNA显示差异分布。
The N-methyl D-aspartate (NMDA) receptor subtype of glutamate-gated ion channels possesses high calcium permeability and unique voltage-dependent sensitivity to magnesium and is modulated by glycine. Molecular cloning identified three complementary DNA species of rat brain, encoding NMDA receptor subunits NMDAR2A (NR2A), NR2B, and NR2C, which are 55 to 70% identical in sequence. These are structurally related, with less than 20% sequence identity to other excitatory amino acid receptor subunits, including the NMDA receptor subunit NMDAR1 (NR1). Upon expression in cultured cells, the new subunits yielded prominent, typical glutamate- and NMDA-activated currents only when they were in heteromeric configurations with NR1. NR1-NR2A and NR1-NR2C channels differed in gating behavior and magnesium sensitivity. Such heteromeric NMDA receptor subtypes may exist in neurons, since NR1 messenger RNA is synthesized throughout the mature rat brain, while NR2 messenger RNA show a differential distribution.