Beck C, Wollmuth L P, Seeburg P H, Sakmann B, Kuner T
Abteilung Molekulare Neurobiologie, Max-Planck-Institut für medizinische Forschung, Heidelbeg, Germany.
Neuron. 1999 Mar;22(3):559-70. doi: 10.1016/s0896-6273(00)80710-2.
In NMDA receptor channels, the M2 loop forms the narrow constriction and the cytoplasmic vestibule. The identity of an extracellular vestibule leading toward the constriction remained unresolved. Using the substituted cysteine accessibility method (SCAM), we identified channel-lining residues of the NR1 subunit in the region preceding M1 (preM1), the C-terminal part of M3 (M3C), and the N-terminal part of M4 (M4N). These residues are located on the extracellular side of the constriction and, with one exception, are exposed to the pore independently of channel activation, suggesting that the gate is at the constriction or further cytoplasmic to it. Permeation of Ca2+ ions was decreased by mutations in M3C and M4N, but not by mutations in preM1, suggesting a functionally distinct contribution of the segments to the extracellular vestibule of the NMDA receptor channel.
在N-甲基-D-天冬氨酸（NMDA）受体通道中，M2环形成狭窄的收缩部和胞质前庭。通向收缩部的细胞外前庭的特征仍未明确。我们使用半胱氨酸替代可及性方法（SCAM），鉴定了M1之前区域（preM1）、M3的C末端部分（M3C）和M4的N末端部分（M4N）中NR1亚基的通道内衬残基。这些残基位于收缩部的细胞外侧，除一个例外，它们独立于通道激活而暴露于孔道，这表明门控位于收缩部或其更靠胞质侧。M3C和M4N中的突变会降低Ca2+离子的通透，但preM1中的突变则不会，这表明这些片段对NMDA受体通道细胞外前庭的功能贡献不同。
