NMDA-RECEPTOR CHANNEL DIVERSITY IN THE DEVELOPING CEREBELLUM
NMDA-RECEPTOR CHANNEL DIVERSITY IN THE DEVELOPING CEREBELLUM
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DOI：
10.1038/368335a0
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发表时间：
1994-03-24
期刊：
影响因子：
64.8
通讯作者：
CULLCANDY, SG
中科院分区：
文献类型：
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作者：
FARRANT, M;FELDMEYER, D;CULLCANDY, SG
在小脑中，NMDA（N-甲基-D-天冬氨酸）受体在神经元分化（1，2）和兴奋性突触传递（3-5）中起重要作用。在小脑发育早期，编码各种NMDA受体亚单位的信使RNA的分布发生了显著变化（6）。为了确定这些变化是否导致功能不同的NMDA受体的出现（7-9），我们记录了大鼠小脑颗粒细胞从外胚层迁移到内颗粒层期间的单通道电流（10）。在这里，我们发现在突触形成之前（10，11），迁移前和迁移颗粒细胞表达具有单通道特性的NMDA受体，类似于先前描述的许多中枢神经元（12，16）。相反，成熟的迁移后细胞也表达一种非典型形式的NMDA受体，具有较低的单通道电导和独特的动力学行为。这些“低电导”通道的特性与对通过NR 1和NR 2C亚基的共表达形成的重组NMDA受体（8，9）所描述的那些（17）相对应。NR 2C亚基在出生后出现，主要在成人小脑中发现（6-8）。我们的数据表明，NMDA受体的特性在单通道水平的发展变化，并建议，是小脑的特定亚基蛋白的表达结果在一个独特的形式的天然受体。
IN the cerebellum, NMDA (N-methyl-D-aspartate) receptors play an important role in neuronal differentiation(1,2) and excitatory synaptic transmission(3-5). During early cerebellar development, marked changes occur in the distribution of messenger RNAs encoding various NMDA-receptor subunits(6). To determine whether these changes result in the appearance of functionally distinct NMDA receptors(7-9), we have recorded single-channel currents in rat cerebellar granule cells during the period of their migration from the external germinal layer to the inner granular layer(10). Here we show that before synapse formation(10,11), pre-migratory and migrating granule cells express NMDA receptors possessing single-channel properties similar to those previously described for many central neurons(12,16). In contrast, mature post-migratory cells also express an atypical form of NMDA receptor that has a lower single-channel conductance and distinct kinetic behaviour. The properties of these 'low-conductance' channels correspond to those described(17) for recombinant NMDA receptors formed by coexpression of NR1 and NR2C subunits(8,9). The NR2C subunit appears postnatally and is found predominantly in the adult cerebellum(6-8). Our data demonstrate developmental changes in NMDA-receptor properties at the single-channel level, and suggest that is the cerebellum the expression of a specific subunit protein results in a distinct form of native receptor.