Tong Chi-Kun, Kaftan Edward J, Macdermott Amy B
Department of Physiology and Cellular Biophysics, Columbia University, New York, New York 10032, USA.
Mol Pain. 2008 Oct 10;4:44. doi: 10.1186/1744-8069-4-44.
NMDA receptors are important elements in pain signaling in the spinal cord dorsal horn. They are heterotetramers typically composed of two NR1 and two of four NR2 subunits: NR2A-2D. Mice lacking specific NR2 subunits show deficits in pain transmission yet subunit location in the spinal cord remains unclear. We have combined electrophysiological and pharmacological approaches to investigate the composition of functional NMDA receptors expressed by lamina I, substance P receptor-expressing (NK1R+) neurons, as well as NK1R- neurons. Under low Mg2+ conditions (100 microM), the conductance of NMDA receptors at -90 mV (g(-90 mV)) with NR2A or NR2B subunits (NR2A/B) is low compared to conductance measured at the membrane potential where the inward current is maximal or maximal inward current (MIC) (ratio of approximately 0.07 calculated from Kuner and Schoepfer, 1996). For NR2C or NR2D subunits (NR2C/D), the ratio is higher (ratio approximately 0.4). NK1R+ and NK1R- neurons express NMDA receptors that give ratios approximately 0.28 and 0.16, respectively, suggesting both types of subunits are present in both populations of neurons, with NK1R+ neurons expressing a higher percentage of NR2C/D type NMDA receptors. This was confirmed using EAB318, an NR2A/B preferring antagonist, and UBP141, a mildly selective NR2C/D antagonist to increase and decrease the g(-90 mV)/g(MIC) ratios in both subpopulations of neurons.
N-甲基-D-天冬氨酸（NMDA）受体是脊髓背角疼痛信号传导中的重要元件。它们是异源四聚体，通常由两个NR1亚基和四个NR2亚基中的两个组成：NR2A - 2D。缺乏特定NR2亚基的小鼠在疼痛传递方面表现出缺陷，但脊髓中亚基的定位仍不清楚。我们结合了电生理学和药理学方法，来研究由I层表达P物质受体（NK1R +）的神经元以及NK1R - 神经元所表达的功能性NMDA受体的组成。在低镁离子（100微摩尔）条件下，与在内向电流最大或最大内向电流（MIC）的膜电位下测得的电导相比，含有NR2A或NR2B亚基（NR2A / B）的NMDA受体在-90 mV时的电导（g（-90 mV））较低（根据库纳和舍普费尔1996年的数据计算，比率约为0.07）。对于NR2C或NR2D亚基（NR2C / D），该比率较高（比率约为0.4）。NK1R +和NK1R - 神经元表达的NMDA受体给出的比率分别约为0.28和0.16，这表明两种类型的亚基都存在于这两类神经元中，其中NK1R +神经元表达的NR2C / D型NMDA受体百分比更高。使用EAB318（一种更倾向于NR2A / B的拮抗剂）和UBP141（一种轻度选择性的NR2C / D拮抗剂）来增加和降低这两类神经元亚群中的g（-90 mV）/ g（MIC）比率，证实了这一点。
