NMDA receptors (NMDAR), glutamate receptors are the predominant molecular device for synaptic plasticity and to control the memory function. NMDAR is a particular type of ionotropic glutamate receptors. Instead of NMDA receptors of NMDA (N-methyl-D-aspartate), is the name of the selective agonists that bind to the receptor “,” glutamate other. Activation of NMDA receptors resulting in the opening of ion channels are non-selective for cations having an equilibrium potential near 0 mV. Obtain a block of the ion channel of Mg2 ions extracellular nature of NMDA receptors is their voltage-dependent activation. This allows the ions is dependent on the voltage and K Ca2 small amount of flow cell and Na out of the cell. Calcium flux is considered important in cellular mechanism for memory and synaptic plasticity, learning and through NMDARs. It is important in two ways of the NMDA receptor. Glycine and D-serine or glutamic acid: First, ligand-dependent and it has been voltage-dependent, and second, it requires the simultaneous activation of the two ligands.
Is an expression glutamate-gated ion channels in the central nervous system (NMDARs) plays an important role in excitatory synaptic transmission enlarge N-methyl-D-aspartate receptors. For his involvement in a number of neurological disorders, NMDARs is the target to be treated. NMDARs occurs in a subtype of some subset of the pharmacological properties and biophysical and its composition is different from that. In particular, have begun to reveal the molecular determinants of the selection of this subset, NMDARs are agents or endogenous ligands are likely to act to modulate the data in the structure and function of the recent and receptor subunit selective, I include some of a variety of objects. Binding site of glutamate, these include the recently identified allosteric site at the N-terminal domain and the pore of the ion channel. At the interface between subunits, potential sites other is unexplored by medicinal chemistry program to be considered also particularly still. Given the growing evidence that implicate subtypes various brain disorders different NMDAR, as NR2B, and interest in the use of pharmacological heterogeneity of NMDARs in the development of novel NMDAR subtype selective compounds in NR3A and pain in damage to the white matter There is growing.
How over-stimulation of excitotoxicity of NMDARs result, contribute and Huntington’s disease and role in the control of the structure and function of neurons and synapses, the brain disorder, progressive some during the development of the initial, this attractive new how to control the level of gene transcription of several families of transcription factors, alcoholism of the central nervous system and functional expression that covers many aspects of the biology of NMDARs is, the treatment of alcoholism this long-term changes in synaptic strength, interaction NMDAR activation of the dopamine receptor and mediated NMDARs rewards, the importance of phosphatase of cellular mechanisms involved in the transport protein kinases and the role of NMDARs in the promise of treatment of NMDAR base for how the physiology how to signal the accumulation of activation cascade of sex, to adjust the local synaptic protein synthesis necessary in the regulation of NMDAR function of the target of NMDAR protein for many, the signal at the synapse and dendritic spines I will control the transfer form NMDAR-mediated calcium, of the spine. NMDARs plays a role in the stage of time different memory formation in Drosophila. Design of therapeutic agents, extracellular modulation NMDARs polyamide, subunit specific inhibitor, the zinc ion, pH, the physiological role and structure-activity relationship, the antagonist structural basis for the effect, NMDAR pharmacology, agonists and a detailed description of the path to the molecular structure of the NMDARs, the role of localization in presynaptic NMDARs to control the possibility of synaptic plasticity for new therapeutic and allosteric modulators and NMDAR activation mechanism.
NMDA receptor subunit is composed of different classes of two. NR1 subunit contains all the properties of the NMDA receptor channel complex while enhancing the NMDA receptor response from hetero-assembly of the NR1 and discrimination (NR2A-2D) 4 NR2 subunit. MRNA of 5 NMDA receptor subunits are expressed in the cerebellum space ways different time. To examine the function of the NMDA receptor in the cerebellum, producing a deficient knockout mice both of these subunits NR2A or NR2C and we. Mutant mice of all three develop normally, I showed a normal overall morphology of the cerebellum. The NR2C-deficient mice and NR2A, NMDA receptor-mediated component in the evaluation of EPSCS granule cells are decreased in eliminating mouse Zu NR2C and NR2A virtually by whole cell recording of brain slices as. NR2C-deficient granule cells and NR2A is different in the time course of NM DA receptor response and the relationship of the DC voltage. NR2A subunit is contributing to the excitatory transmission via NMDA-receptors in different granule cells of mossy fiber synapses mature cerebellum and NR2C like this. Both of NR2C-deficient mice and NR2A is to test motor coordination task, movement of impairment was observed. The NR2C-deficient mutant mice and NR2A, you can stay in a stationary like this, to manage a simple coordination tasks, such as rotating the rod slowly, staying to rotate the rod rapidly such, more challenging You can fail to. The NMDA receptor, these data suggest that it plays an active role in motor coordination.
The NMDA receptor, NR2 subunits two regions and localized two duty NR1 subunits form a heterotetramer of (has been identified as NR2 subunits NR1) subunits and two GluN1 GluN2 two. When you link to gene family of B subunit and NR3 A, it has an inhibitory effect on the activity of the receptor. receptor isoforms with multiple functional properties and brain distribution of different caused by alternative splicing of the expression of contrast of NR2 subunits and NR1 transcription. It has a modular design, each structural module, each receptor subunit represents a functional module:
- Ligand-binding domain and modulation domain: the extracellular domain, which contains the structure of two spherical. NR2 subunit binding and glycine co-agonist site on the NR1 subunit binds glutamate neurotransmitter.
- Agonist binding module connection membrane domain is similar to the selectivity filter of potassium channels are composed of reentrant loop 3 and transmembrane segment.
- Membrane area is responsible for the high conductivity of a single receptor that contribute to the residual of the channel pore, with a voltage-dependent block of magnesium transparency and high calcium.
- Each subunit has a cytoplasmic domain containing residues that may not be modified by a number of interacting residues adapter scaffold protein phosphatase and many protein kinases, and structural proteins directly.
The glutamate-binding module NR2A subunits and NR3 subunits NR1 and glycine binding components, after expression as a soluble protein, by X-ray crystallography, three-dimensional structure thereof, has been solved at atomic resolution. This indicated amino acids twice bind common glutamate binding module AMPA receptors and bacterial protein and the kainate receptor.
Activation of NMDA receptors requires the binding of (unstimulated aspartate receptor by strong) aspartic acid and glutamic acid. In addition, also NMDARs is, it requires the binding of the co-agonist glycine for the effective detection of ion channel that is part of the receptor. The D-serine, agonize that the NMDA receptor with a large force has been further found glycine both. It is produced by serine racemase, D-serine is concentrated in the same area and the NMDA receptor. D-serine, and delete it will be able to block NMDA-mediated excitatory neurotransmission in many areas. Recently, D-serine, it is possible to release the control of NMDA receptors from both astrocytes and neurons is shown. Further, the third requirement is a membrane depolarization.
The positive change in membrane potential, the ion channel of the NMDA receptor, likely to open in the expulsion of Mg2 ions to block the channel from the outside will be higher. This property is essential for the role of NMDA receptors in learning and memory, the channel, it is assumed to be a biochemical substrate Hebbian learning that it can act as synaptic transmission and depolarization of the match detection membrane to.