Ionotropic glutamate receptors in the CNS excitatory synapses of vertebrates are involved in numerous physiological and pathological processes. Decades of intensive studies greatly advanced our understanding of molecular organization of these transmembrane proteins. Here we focus on the channel pore domain, its selectivity filter and the activation gate, and the pore block by organic ligands. We compare findings from indirect experimental approaches, including site-directed mutagenesis, with recent crystal and cryo-EM structures of different channels in different functional states and complexed with different ligands. We summarize remaining uncertainties and unresolved problems related to the channel structure, function and pharmacology.

脊椎动物中枢神经系统兴奋性突触中的离子型谷氨酸受体参与许多生理和病理过程。数十年的深入研究极大地增进了我们对这些跨膜蛋白分子组织的理解。在这里，我们关注通道孔结构域，其选择性过滤器和激活门以及有机配体对孔的阻塞。我们将间接实验方法（包括定点诱变）与不同功能状态下的不同通道的最新晶体和低温电磁结构进行比较，并与不同的配体复合。我们总结了与通道结构，功能和药理学有关的不确定性和未解决的问题。