Increased exon 5 expression alters extrasynaptic NMDA receptors in cerebellar neurons.

Increased exon 5 expression alters extrasynaptic NMDA receptors in cerebellar neurons.
复制标题

外显子 5 表达增加会改变小脑神经元的突触外 NMDA 受体。

DOI:
10.1046/j.1471-4159.2000.0751140.x
复制
发表时间:
2000
影响因子:
4.7
通讯作者:
Vicini,S
Vicini,S
中科院分区:
医学2区
文献类型:
--
作者:
Prybylowski,K;Rumbaugh,G;Wolfe,BB;Vicini,S

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翻译后摘要:我们研究了个体发育的变化,在表达的选择性剪接形式的NR1蛋白,包含N1盒(外显子5)在大鼠小脑内的NR1的总人口相比。N1盒在小脑中受到强烈的发育调控,成年大鼠中超过80%的总NR1蛋白含有N1盒。相比之下,在发育早期,<20%的NR1蛋白含有该盒。来自相同年龄的大鼠皮质没有显示表达N1盒的NR1蛋白百分比增加,表明小脑的发育变化具有组织特异性。由于已知N1盒可确定NMDA受体特性,包括精胺敏感性和谷氨酸诱导电流的衰减动力学,因此在出生后第7天与第14天比较了小脑切片颗粒细胞中谷氨酸激活电流特征的变化。第14天,谷氨酸反应表现出快速失活动力学和精胺的增强作用降低,同时保持对NR 2B选择性拮抗剂的敏感性。这些数据是一致的可能性,N1盒的表达可能是一个因素,在突触外NMDA受体在小脑的属性的发展变化。
Abstract:We investigated the ontogenic changes in expression of alternatively spliced forms of NR1 protein that contain the N1 cassette (exon 5) in comparison with the total population of NR1 within the rat cerebellum. The N1 cassette is strongly developmentally regulated in the cerebellum, with >80% of total NR1 protein in the adult rat containing the N1 cassette. In contrast, early in development, <20% of NR1 protein contained this cassette. Rat cortices from the same ages did not show an increase in the percent of NR1 protein expressing the N1 cassette, indicating that the developmental changes in the cerebellum are tissue‐specific. As the N1 cassette is known to determine NMDA receptor properties, including spermine sensitivity and decay kinetics of glutamate‐induced currents, changes in the characteristics of glutamate‐activated currents in granule cells from cerebellar slices were compared at postnatal day 7 versus 14. Glutamate responses exhibited fast deactivation kinetics and reduced potentiation by spermine at day 14 while maintaining sensitivity to an NR2B‐selective antagonist. These data are consistent with the possibility that N1 cassette expression may be a factor in the developmental changes in properties of extrasynaptic NMDA receptors in the cerebellum.