Agonist-specific gating of NMDA receptors.
Agonist-specific gating of NMDA receptors.
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DOI：
10.4161/chan.4.2.10523
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发表时间：
2010-03
期刊：
影响因子：
--
通讯作者：
Popescu GK
中科院分区：
文献类型：
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作者：
Kussius CL;Popescu AM;Popescu GK
配体结合在细胞外受体区域打开跨膜离子传导孔的机制尚不清楚。在具有不同功效的激动剂存在的情况下，检查通道的激活反应可能会告知这个问题，并可能有助于确定激动剂依赖的转变。我们最近将这种方法应用于GluN1和GluN2A亚基组成的NMDA受体。基于我们对几种亚基特异性部分激动剂的研究结果，我们得出结论，激动剂的作用分布在构成NMDA受体门控的几种多重转变中，并且这些变化是亚基独立的。在这里，我们研究了另一种GluN2A部分激动剂，4-氟- d， l -谷氨酸，并总结了所研究的所有9种部分激动剂的动力学变化。这些结果支持了一个前提，即无论它们结合的亚基类型如何，激动剂都会影响NMDA受体反应中的多个平衡，并可能稳定稍微不同的构象家族。
The mechanism by which ligand binding at extracellular receptor domains gates a transmembrane ion-conducting pore is insufficiently understood. Examining a channel’s activation reaction in the presence of agonists with distinct efficacies may inform this issue and may help identify agonist-dependent transitions. We have recently applied this approach to NMDA receptors composed of GluN1 and GluN2A subunits. Based on our results with several subunit-specific partial agonists we concluded that agonist effects were distributed over several of the multiple transitions that make up NMDA receptor gating and that these changes were subunit independent. Here we examine an additional GluN2A partial agonist, 4-fluoro-D, L-glutamic acid, and we summarize the observed kinetic changes of all nine partial agonists investigated. These results support the premise that regardless of the subunit-type to which they bind, agonists influence multiple equilibria within the NMDA receptor reaction and may stabilize a slightly different family of conformers.