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The N-methyl-D-aspartate receptor (also known as the NMDA receptor or NMDAR), is a glutamate receptor and ion channel protein found in nerve cells. It is activated when glutamate and glycine (or D-serine) bind to it, and when activated it allows positively charged ions to flow through the cell membrane. The NMDA receptor is very important for controlling synaptic plasticity and memory function. The NMDAR is a specific type of ionotropic glutamate receptor. The NMDA receptor is named this because the agonist molecule ''N''-methyl-D-aspartate (NMDA) binds selectively to it, and not to other glutamate receptors. Activation of NMDA receptors results in the opening of an ion channel that is nonselective to cations with a reversal potential near 0 mV. A property of the NMDA receptor is its voltage-dependent activation, a result of ion channel block by extracellular Mg2+ & Zn2+ ions. This allows the flow of Na+ and small amounts of Ca2+ ions into the cell and K+ out of the cell to be voltage-dependent. Calcium flux through NMDARs is thought to be critical in synaptic plasticity, a cellular mechanism for learning and memory. The NMDA receptor is distinct in two ways: first, it is both ligand-gated and voltage-dependent; second, it requires co-activation by two ligands: glutamate and either D-serine or glycine. The activity of the NMDA receptor is affected by many psychoactive drugs such as phencyclidine (PCP), alcohol (ethanol) and dextromethorphan (DXM). The anaesthetic effects of the drugs ketamine and nitrous oxide are partially because of their effects on NMDA receptor activity. ==Structure== The NMDA receptor forms a heterotetramer between two GluN1 and two GluN2 subunits (the subunits were previously denoted as NR1 and NR2), two obligatory NR1 subunits and two regionally localized NR2 subunits. A related gene family of NR3 A and B subunits have an inhibitory effect on receptor activity. Multiple receptor isoforms with distinct brain distributions and functional properties arise by selective splicing of the NR1 transcripts and differential expression of the NR2 subunits. Each receptor subunit has modular design and each structural module also represents a functional unit: * The ''extracellular domain'' contains two globular structures: a modulatory domain and a ligand-binding domain. NR1 subunits bind the co-agonist glycine and NR2 subunits bind the neurotransmitter glutamate. * The ''agonist-binding module'' links to a membrane domain, which consists of three trans-membrane segments and a re-entrant loop reminiscent of the selectivity filter of potassium channels. * The ''membrane domain'' contributes residues to the channel pore and is responsible for the receptor's high-unitary conductance, high-calcium permeability, and voltage-dependent magnesium block. * Each subunit has an extensive ''cytoplasmic domain'', which contain residues that can be directly modified by a series of protein kinases and protein phosphatases, as well as residues that interact with a large number of structural, adaptor, and scaffolding proteins. The glycine-binding modules of the NR1 and NR3 subunits and the glutamate-binding module of the NR2A subunit have been expressed as soluble proteins, and their three-dimensional structure has been solved at atomic resolution by x-ray crystallography. This has revealed a common fold with amino acid-binding bacterial proteins and with the glutamate-binding module of AMPA-receptors and kainate-receptors. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「NMDA receptor」の詳細全文を読む スポンサード リンク
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