Wollmuth Lonnie P
Department of Neurobiology & Behavior and Biochemistry & Cell Biology, Center for Nervous System Disorders, Stony Brook University, Stony Brook, NY 11794-5230.
Curr Opin Physiol. 2018 Apr;2:36-41. doi: 10.1016/j.cophys.2017.12.003. Epub 2017 Dec 19.
Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that mediate the vast majority of fast synaptic transmission in the nervous system. When the iGluR ion channel is in the open or conducting conformation, it is non-selective for monovalent cations, driving membrane excitation. Often the channel is also permeable to Ca. This process of Ca permeation and its physiological and pathological consequences depend strongly on the specific iGluR subtype as well as the specific subunits in the oligomeric complex. Recent evidence has highlighted additional levels of diversity to this process including a dependence on specific auxiliary subunits in non-NMDARs and post-translational modifications in NMDARs. Various missense mutations associated with neurological disease in NMDAR subunits have been identified in regions critical to Ca influx. These features highlight the dynamics of Ca influx mediated by iGluRs and its critical role in synaptic physiology and pathology.
离子型谷氨酸受体（iGluRs）是配体门控离子通道，介导神经系统中绝大多数快速突触传递。当iGluR离子通道处于开放或传导构象时，它对单价阳离子无选择性，驱动膜兴奋。该通道通常也对Ca通透。Ca通透过程及其生理和病理后果在很大程度上取决于特定的iGluR亚型以及寡聚复合物中的特定亚基。最近的证据突出了该过程的更多层次的多样性，包括对非NMDA受体中特定辅助亚基的依赖性以及NMDA受体中的翻译后修饰。在对Ca内流至关重要的区域已鉴定出与NMDA受体亚基中神经疾病相关的各种错义突变。这些特征突出了由iGluRs介导的Ca内流的动态变化及其在突触生理和病理中的关键作用。
