Farrant M, Feldmeyer D, Takahashi T, Cull-Candy S G
Department of Pharmacology, University College London, UK.
Nature. 1994 Mar 24;368(6469):335-9. doi: 10.1038/368335a0.
In the cerebellum, NMDA (N-methyl-D-aspartate) receptors play an important role in neuronal differentiation and excitatory synaptic transmission. During early cerebellar development, marked changes occur in the distribution of messenger RNAs encoding various NMDA-receptor subunits. To determine whether these changes result in the appearance of functionally distinct NMDA receptors, 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. Here we show that before synapse formation, pre-migratory and migrating granule cells express NMDA receptors possessing single-channel properties similar to those previously described for many central neurons. 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 for recombinant NMDA receptors formed by coexpression of NR1 and NR2C subunits. The NR2C subunit appears postnatally and is found predominantly in the adult cerebellum. Our data demonstrate developmental changes in NMDA-receptor properties at the single-channel level, and suggest that in the cerebellum the expression of a specific subunit protein results in a distinct form of native receptor.
在小脑中，N-甲基-D-天冬氨酸（NMDA）受体在神经元分化和兴奋性突触传递中发挥重要作用。在小脑发育早期，编码各种NMDA受体亚基的信使核糖核酸的分布发生显著变化。为了确定这些变化是否导致功能上不同的NMDA受体出现，我们在大鼠小脑颗粒细胞从外颗粒层迁移到内颗粒层的期间记录了单通道电流。我们在此表明，在突触形成之前，迁移前和迁移中的颗粒细胞表达的NMDA受体具有与先前许多中枢神经元所描述的单通道特性相似的特性。相比之下，成熟的迁移后细胞还表达一种非典型形式的NMDA受体，其单通道电导较低且具有独特的动力学行为。这些“低电导”通道的特性与由NR1和NR2C亚基共表达形成的重组NMDA受体所描述的特性相符。NR2C亚基在出生后出现，主要存在于成年小脑中。我们的数据证明了NMDA受体特性在单通道水平上的发育变化，并表明在小脑中特定亚基蛋白的表达导致了一种独特形式的天然受体。
