冷泉港实验室Hiro Furukawa团队宣布他们研制了NMDA受体钙通透性和镁阻滞的分子机制。相关论文于2026年5月5日发表在《自然—神经科学》杂志上。

在这里，该课题组展示了主题的单粒子低温电子显微镜，Ca²⁺渗透通过狭窄的收缩阳离子选择性过滤器涉及部分脱水，证明了几个Ca²⁺结合位点。相反，Mg²⁺通过水网络结合在选择性过滤器外并保持水合状态，从而起到通道阻滞剂的作用。

此外，选择性过滤器周围的脂质网络以电压依赖的方式影响Mg²⁺结合的稳定性。他们的研究详细说明了启动神经可塑性所必需的跨膜化学。

据悉，Hebbian神经可塑性被认为是学习和记忆的细胞基质，它可以通过突触前神经递质释放和突触后去极化时Ca²⁺内流的巧合检测而发生。这是由N-甲基-D-天冬氨酸型谷氨酸受体在分子水平上介导的，该受体结合谷氨酸和甘氨酸，并在膜去极化过程中缓解Mg²⁺通道阻塞时促进Ca²⁺内流。然而，N-甲基-D-天冬氨酸型谷氨酸受体Ca²⁺通透性和Mg²⁺阻断的结构机制尚未完全阐明。

附：英文原文

Title: Molecular mechanism of calcium permeability and magnesium block in NMDA receptors

Author: Steigerwald, Ruben, Epstein, Max, Chou, Tsung-Han, Simorowski, Noriko, Furukawa, Hiro

Issue&Volume: 2026-05-05

Abstract: Hebbian neuroplasticity, which is thought to be a cellular substrate of learning and memory, can occur by means of coincidental detection of presynaptic neurotransmitter release and Ca2+ influx upon postsynaptic depolarization. This is mediated at a molecular level by N-methyl-D-aspartate-type glutamate receptors, which bind glutamate and glycine and facilitate Ca2+ influx upon relief of Mg2+ channel block during membrane depolarization. However, the structural mechanism underlying Ca2+ permeability and Mg2+ blockade in N-methyl-D-aspartate-type glutamate receptors has yet to be fully elucidated. Here we demonstrate using single-particle cryo-electron microscopy that Ca2+ permeation through the narrow constriction of the cation selectivity filter involves partial dehydration, as evidenced by several Ca2+ binding sites. In contrast, Mg2+ binds outside of the selectivity filter through a water network and remains hydrated, thereby acting as a channel blocker. Furthermore, the lipid network around the selectivity filter influences the stability of Mg2+ binding in a voltage-dependent manner. Our study details the transmembrane chemistry essential for initiating neuroplasticity.

DOI: 10.1038/s41593-026-02283-3

Source: https://www.nature.com/articles/s41593-026-02283-3