NMDARs receptors

NMD A receptors are selectively activated by A/-methyl-D-aspartate (NMD A) (182). NMD A receptor activation also requires glycine or other co-agonist occupation of an allosteric site. NMDAR-1, -2A, -2B, -2C, and -2D are the five NMD A receptor subunits known. Two forms of NMDAR-1 are generated by alternative splicing. NMDAR-1 proteins form homomeric ionotropic receptors in expression systems and may do so m situ in the CNS. Functional responses, however, are markedly augmented by co-expression of a NMDAR-2 and NMDAR-1 subunits. The kinetic and pharmacological properties of the NMD A receptor are influenced by the particular subunit composition. 

Monyer H, Jonas P, Rossier J (1999) Molecular determinants controlling functional properties of AMPARs and NMDARs in the mammalian CNS, chapter 9 Ionotropic glutamate receptors in the CNS. Springer Verlag... 

NMDAR. An ionotropic receptor for glutamate. It plays a critical role in synaptic plasticity mechanisms and thus is necessary for several types of learning and memory. 

Thus, the mechanistic properties of the NMDA receptor can help account for the properties of temporal specificity, cooperativity, and associativity of LTP. They can also explain why both high-frequency stimulation (100 Hz) and pairing low-frequency stimulation with postsynaptic depolarization can induce LTP. The occurrence of presynaptic activity followed by postsynaptic activity determines a temporal sequence and specificity. To generate sufficient depolarization in the postsynaptic cell to expel Mg2+ from NMDAR channels usually requires cooperative depolarization at many synapses. Moreover, the requirement of postsynaptic depolarization also underlies associativity since the depolarization caused by the strongly activated synapses can relieve the Mg2+ blockade of the NMDA receptors on weakly activated synapses. 

HTxR, serotonin receptor CB1R, cannabinoid-1 DAT, dopamine transporter GABA, y-aminobutyric acid Kir3 channels, G protein-coupled inwardly rectifying potassium channels LSD, lysergic acid diethylamide i -OR, H-opioid receptor nAChR, nicotinic acetylcholine receptor NET, norepinephrine transporter NMDAR, N -methyl-D-aspartate receptor SERT, serotonin transporter VMAT, vesicular monoamine transporter indicates data not available. 

Zimmer, M., Fink, T. M., Franke, Y., Lichter, P., Spiess, J. Cloning and structure of the gene encoding the human NMDA receptor (NMDAR-1), Gene 1995, 159, 219-223. 

NR1 is a component of all native NMDA receptors. The NRI subunit is the glycine binding subunit. It exists as 8 splice variants of a single gene. C-terminal deletion of the NRI subunit causes NMDAR inactivation, changes in downstream... 

One of the first observations we made was that Ca2+-induced Ca2+ release from intracellular stores mediates an important component of mossy fiber LTP and synaptic facilitation (Lauri et al., 2003). This was achieved by treatments that inhibited Ca2+ release from intracellular stores and by philanthotoxin, which blocks Ca2+ permeable receptors. These results suggest that the necessary trigger for Ca2+ release from internal stores can be provided by Ca2+ entry through Ca2+-permeable KARs. The magnification of the synaptic Ca2+ transient by release of Ca2+ from intracellular stores has previously been described in hippocampal CA1 neurons (Alford et al., 1993 Emptage et al., 1999) and is the element that triggers an intracellular cascade involved in the induction of LTP, at least under certain experimental conditions. Thus, there are parallels between NMDAR- and KAR-dependent LTP at the level of Ca2+ release from intracellular stores. 

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