Zarei M M, Dani J A
Division of Neuroscience, Baylor College of Medicine, Houston, Texas 77030-3.
J Neurosci. 1995 Feb;15(2):1446-54. doi: 10.1523/JNEUROSCI.15-02-01446.1995.
The open-channel structure of the N-methyl-D-aspartate (NMDA) receptor was investigated to explain apparently conflicting interpretations about ionic interactions within the pore. Patch-clamp techniques were applied to tissue-cultured rat hippocampal neurons from the CA1 region. A wide range of ammonium derivatives was studied to learn about the structure of the pore from permeability and open-channel blocking characteristics. We conclude that the pore is asymmetric, having high-affinity binding for organic cations from the outside and having a larger external entrance. The minimum cross-sectional area of the pore is rectangular (approximately 0.45 x 0.57 nm) and is the single-occupancy binding site(s) for small permeant cations. The narrow region extending from this minimum cross section is short, and its shape underlies the voltage dependencies of blocking cations. While occupying the blocking site, some open-channel blockers can interact with permeant cations at their binding site in the minimum cross section. A structurally based hypothesis is presented, explaining that the electrostatic interactions between the blocking site and permeant-ion site produce a high voltage dependence for blockade by some cations.
对N-甲基-D-天冬氨酸（NMDA）受体的开放通道结构进行了研究，以解释关于孔内离子相互作用的明显相互矛盾的解释。膜片钳技术应用于来自CA1区的组织培养大鼠海马神经元。研究了多种铵衍生物，以从通透性和开放通道阻断特性了解孔的结构。我们得出结论，孔是不对称的，对来自外部的有机阳离子具有高亲和力结合，并且具有较大的外部入口。孔的最小横截面积为矩形（约0.45×0.57nm），是小通透阳离子的单占据结合位点。从这个最小横截面延伸的狭窄区域很短，其形状是阻断阳离子电压依赖性的基础。在占据阻断位点时，一些开放通道阻断剂可以在最小横截面的结合位点与通透阳离子相互作用。提出了一个基于结构的假设，解释了阻断位点与通透离子位点之间的静电相互作用导致一些阳离子的阻断具有高电压依赖性。
