Distinct functional and pharmacological properties of Triheteromeric GluN1/GluN2A/GluN2B NMDA receptors.
Distinct functional and pharmacological properties of Triheteromeric GluN1/GluN2A/GluN2B NMDA receptors.
复制标题
DOI：
10.1016/j.neuron.2014.01.035
复制
发表时间：
2014-03-05
期刊：
影响因子：
16.2
通讯作者：
Traynelis SF
中科院分区：
文献类型：
--
作者：
Hansen KB;Ogden KK;Yuan H;Traynelis SF
NMDA受体是由GluN1、GluN2和GluN3亚基组成的四聚体配体门控离子通道。在大多数表达NMDA受体的细胞中发现了两种不同的GluN2亚基，大多数天然受体是含有两种GluN1和两种不同GluN2的三异构体。与二异聚体的NMDA受体相比，三异聚体的功能知之甚少。我们开发了一种方法，在细胞表面选择性表达重组GluN1/GluN2A/GluN2B三异构体，并将这些受体与GluN1/GluN2A和GluN1/GluN2B二异构体的特性进行了比较。我们发现谷氨酸失活的三异构体不同于GluN1/GluN2A和GluN1/GluN2B，并揭示了亚单位选择性拮抗剂伊芬地尔、CP-101,606、TCN-201和细胞外Zn2+对三异构体的调节。此外，动力学测量表明，与GluN1/GluN2B双异构体相比，三异构体的伊芬普罗地尔结合位点有所不同。这项工作为GluN1/GluN2A/GluN2B三异构体的独特特性提供了新的见解，这些异构体可能是成人前脑中最丰富的NMDA受体。
NMDA receptors are tetrameric ligand-gated ion channels comprised of GluN1, GluN2, and GluN3 subunits. Two different GluN2 subunits have been identified in most NMDA receptor-expressing cells, and the majority of native receptors are triheteromers containing two GluN1 and two different GluN2. In contrast to diheteromeric NMDA receptors, little is known about the function of triheteromers. We developed a method to provide selective cell-surface expression of recombinant GluN1/GluN2A/GluN2B triheteromers, and compared properties of these receptors with those of GluN1/GluN2A and GluN1/GluN2B diheteromers. We show that glutamate deactivation of triheteromers is distinct from those of GluN1/GluN2A and GluN1/GluN2B, and reveal modulation of triheteromers by subunit-selective antagonists ifenprodil, CP-101,606, TCN-201, and extracellular Zn2+. Furthermore, kinetic measurements suggest variation in the ifenprodil binding site of triheteromers compared to GluN1/GluN2B diheteromers. This work provides new insight to the distinct properties of GluN1/GluN2A/GluN2B triheteromers, which are presumably the most abundant NMDA receptors in the adult forebrain.
登录
查看更多内容
影响因子：
16.2
作者：
Gray JA;Shi Y;Usui H;During MJ;Sakimura K;Nicoll RA
通讯作者：
Nicoll RA
影响因子：
5.3
作者：
Cathala, L;Misra, C;Cull-Candy, S
通讯作者：
Cull-Candy, S
影响因子：
16.2
作者：
Hatton, CJ;Paoletti, P
通讯作者：
Paoletti, P
影响因子：
16.2
作者：
CLEMENTS, JD;WESTBROOK, GL
通讯作者：
WESTBROOK, GL
影响因子：
3.3
作者：
Brock, C;Boudier, L;Pin, JP
通讯作者：
Pin, JP