Ogita K, Kuramoto N, Yoneda Y
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University.
Nihon Rinsho. 1998 Jul;56(7):1819-23.
Ionotropic glutamate receptors are nowadays classified into two major categories based on the sensitivity to N-methyl-D-aspartic acid(NMDA) in the mammalian central nervous system. The NMDA channel has much higher permeability to Ca2+ than the non-NMDA channels in most situations, while point mutation could lead to increased permeation of Ca2+ across the non-NMDA channels. Opening of the NMDA channel is under control by a variety of endogenous low molecules, including glycine, polyamines, Mg2+, Zn2+ and H+, in addition to modulation by Ca2+/calmodulin, protein kinases and protein phosphatases. Moreover, the NMDA channel contains a redox site modulatory for the opening. Recent molecular cloning studies have revealed that the NMDA channel is a protein complex consisting of different subunits such as NMDAR1 and NMDAR2 with heterologous expression in the brain. Studies on mice knocked out of a particular gene argue in favor of an essential role of the corresponding subunits in molecular mechanisms underlying neuronal network formation and synaptic plasticity.
如今,离子型谷氨酸受体在哺乳动物中枢神经系统中根据对N-甲基-D-天冬氨酸(NMDA)的敏感性被分为两大类。在大多数情况下,NMDA通道对Ca2+的通透性比非NMDA通道高得多,而点突变可能导致Ca2+通过非NMDA通道的通透性增加。NMDA通道的开放受多种内源性小分子的控制,包括甘氨酸、多胺、Mg2+、Zn2+和H+,此外还受Ca2+/钙调蛋白、蛋白激酶和蛋白磷酸酶的调节。此外,NMDA通道含有一个对开放起调节作用的氧化还原位点。最近的分子克隆研究表明,NMDA通道是一种蛋白质复合体,由不同的亚基组成,如NMDAR1和NMDAR2,并在大脑中进行异源表达。对敲除特定基因的小鼠的研究支持相应亚基在神经网络形成和突触可塑性的分子机制中起重要作用。