Editing NMDA receptor (section)

====Examples====
The NMDA receptor is modulated by a number of [[endogenous]] and [[exogenous]] compounds:<ref name="pmid15670959">{{cite journal | vauthors = Huggins DJ, Grant GH | title = The function of the amino terminal domain in NMDA receptor modulation | journal = Journal of Molecular Graphics & Modelling | volume = 23 | issue = 4 | pages = 381–388 | date = January 2005 | pmid = 15670959 | doi = 10.1016/j.jmgm.2004.11.006 | bibcode = 2005JMGM...23..381H }}</ref>
* [[Aminoglycoside]]s have been shown to have a similar effect to polyamines, and this may explain their neurotoxic effect.
* [[CDK5]] regulates the amount of [[NR2B]]-containing NMDA receptors on the synaptic membrane, thus affecting [[synaptic plasticity]].<ref name="pmid17529984">{{cite journal | vauthors = Hawasli AH, Benavides DR, Nguyen C, Kansy JW, Hayashi K, Chambon P, Greengard P, Powell CM, Cooper DC, Bibb JA | display-authors = 6 | title = Cyclin-dependent kinase 5 governs learning and synaptic plasticity via control of NMDAR degradation | journal = Nature Neuroscience | volume = 10 | issue = 7 | pages = 880–886 | date = July 2007 | pmid = 17529984 | pmc = 3910113 | doi = 10.1038/nn1914 }}</ref><ref name="pmid18184784">{{cite journal | vauthors = Zhang S, Edelmann L, Liu J, Crandall JE, Morabito MA | title = Cdk5 regulates the phosphorylation of tyrosine 1472 NR2B and the surface expression of NMDA receptors | journal = The Journal of Neuroscience | volume = 28 | issue = 2 | pages = 415–424 | date = January 2008 | pmid = 18184784 | pmc = 6670547 | doi = 10.1523/JNEUROSCI.1900-07.2008 }}</ref>
* [[Polyamine]]s do not directly activate NMDA receptors, but instead act to potentiate or inhibit glutamate-mediated responses.
* [[Reelin]] modulates NMDA function through [[Src Family Kinases|Src family kinases]] and [[DAB1]].<ref name="pmid16148228">{{cite journal | vauthors = Chen Y, Beffert U, Ertunc M, Tang TS, Kavalali ET, Bezprozvanny I, Herz J | title = Reelin modulates NMDA receptor activity in cortical neurons | journal = The Journal of Neuroscience | volume = 25 | issue = 36 | pages = 8209–8216 | date = September 2005 | pmid = 16148228 | pmc = 6725528 | doi = 10.1523/JNEUROSCI.1951-05.2005 }}</ref> significantly enhancing [[Long-term potentiation|LTP]] in the [[hippocampus]].
* [[Src (gene)|Src]] kinase enhances NMDA receptor currents.<ref name="pmid9005855">{{cite journal | vauthors = Yu XM, Askalan R, Keil GJ, Salter MW | title = NMDA channel regulation by channel-associated protein tyrosine kinase Src | journal = Science | volume = 275 | issue = 5300 | pages = 674–678 | date = January 1997 | pmid = 9005855 | doi = 10.1126/science.275.5300.674 | s2cid = 39275755 }}</ref>
* [[Sodium|Na<sup>+</sup>]], [[K ion (physiology)|K<sup>+</sup>]] and [[Ca ion (physiology)|Ca<sup>2+</sup>]] not only pass through the NMDA receptor channel but also modulate the activity of NMDA receptors.<ref>{{cite journal | vauthors = Petrozziello T, Boscia F, Tedeschi V, Pannaccione A, de Rosa V, Corvino A, Severino B, Annunziato L, Secondo A | display-authors = 6 | title = Na<sup>+</sup>/Ca<sup>2+</sup> exchanger isoform 1 takes part to the Ca<sup>2+</sup>-related prosurvival pathway of SOD1 in primary motor neurons exposed to beta-methylamino-L-alanine | journal = Cell Communication and Signaling | volume = 20 | issue = 1 | pages = 8 | date = January 2022 | pmid = 35022040 | pmc = 8756626 | doi = 10.1186/s12964-021-00813-z | doi-access = free }}</ref>
* [[Zinc#Biological role|Zn<sup>2+</sup>]] and [[Copper|Cu<sup>2+</sup>]] generally block NMDA current activity in a noncompetitive and a voltage-independent manner. However zinc may potentiate or inhibit the current depending on the neural activity.<ref>{{cite journal | vauthors = Horning MS, Trombley PQ | title = Zinc and copper influence excitability of rat olfactory bulb neurons by multiple mechanisms | journal = Journal of Neurophysiology | volume = 86 | issue = 4 | pages = 1652–1660 | date = October 2001 | pmid = 11600628 | doi = 10.1152/jn.2001.86.4.1652 | s2cid = 6141092 }}</ref>
* [[Lead|Pb]]<sup>2+</sup><ref>{{cite journal | vauthors = Neal AP, Stansfield KH, Worley PF, Thompson RE, Guilarte TR | title = Lead exposure during synaptogenesis alters vesicular proteins and impairs vesicular release: potential role of NMDA receptor-dependent BDNF signaling | journal = Toxicological Sciences | volume = 116 | issue = 1 | pages = 249–263 | date = July 2010 | pmid = 20375082 | pmc = 2886862 | doi = 10.1093/toxsci/kfq111 }}</ref> is a potent NMDAR antagonist. Presynaptic deficits resulting from Pb<sup>2+</sup> exposure during synaptogenesis are mediated by disruption of NMDAR-dependent BDNF signaling.
* Proteins of the [[major histocompatibility complex]] class I are endogenous negative regulators of NMDAR-mediated currents in the adult hippocampus,<ref name="pmid21135233">{{cite journal | vauthors = Fourgeaud L, Davenport CM, Tyler CM, Cheng TT, Spencer MB, Boulanger LM | title = MHC class I modulates NMDA receptor function and AMPA receptor trafficking | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 51 | pages = 22278–22283 | date = December 2010 | pmid = 21135233 | pmc = 3009822 | doi = 10.1073/pnas.0914064107 | doi-access = free | bibcode = 2010PNAS..10722278F }}</ref> and are required for appropriate NMDAR-induced changes in [[AMPAR]] trafficking <ref name="pmid21135233"/> and NMDAR-dependent [[synaptic plasticity]] and [[learning]] and [[memory]].<ref name="pmid11118151">{{cite journal | vauthors = Huh GS, Boulanger LM, Du H, Riquelme PA, Brotz TM, Shatz CJ | title = Functional requirement for class I MHC in CNS development and plasticity | journal = Science | volume = 290 | issue = 5499 | pages = 2155–2159 | date = December 2000 | pmid = 11118151 | pmc = 2175035 | doi = 10.1126/science.290.5499.2155 | bibcode = 2000Sci...290.2155H }}</ref><ref>{{cite journal | vauthors = Nelson PA, Sage JR, Wood SC, Davenport CM, Anagnostaras SG, Boulanger LM | title = MHC class I immune proteins are critical for hippocampus-dependent memory and gate NMDAR-dependent hippocampal long-term depression | journal = Learning & Memory | volume = 20 | issue = 9 | pages = 505–517 | date = September 2013 | pmid = 23959708 | pmc = 3744042 | doi = 10.1101/lm.031351.113 }}</ref>
* The activity of NMDA receptors is also strikingly sensitive to the changes in [[pH]], and partially inhibited by the ambient concentration of H<sup>+</sup> under physiological conditions.<ref>{{cite journal | vauthors = Traynelis SF, Cull-Candy SG | title = Proton inhibition of N-methyl-D-aspartate receptors in cerebellar neurons | journal = Nature | volume = 345 | issue = 6273 | pages = 347–350 | date = May 1990 | pmid = 1692970 | doi = 10.1038/345347a0 | s2cid = 4351139 | bibcode = 1990Natur.345..347T }}</ref> The level of inhibition by H<sup>+</sup> is greatly reduced in receptors containing the NR1a subtype, which contains the positively charged insert Exon 5. The effect of this insert may be mimicked by positively charged polyamines and aminoglycosides, explaining their mode of action.
* NMDA receptor function is also strongly regulated by chemical reduction and oxidation, via the so-called "redox modulatory site."<ref name="pmid2696504">{{cite journal | vauthors = Aizenman E, Lipton SA, Loring RH | title = Selective modulation of NMDA responses by reduction and oxidation | journal = Neuron | volume = 2 | issue = 3 | pages = 1257–1263 | date = March 1989 | pmid = 2696504 | doi = 10.1016/0896-6273(89)90310-3 | s2cid = 10324716 }}</ref> Through this site, reductants dramatically enhance NMDA channel activity, whereas oxidants either reverse the effects of reductants or depress native responses. It is generally believed that NMDA receptors are modulated by endogenous redox agents such as [[glutathione]], [[lipoic acid]], and the essential nutrient [[pyrroloquinoline quinone]].<ref>{{Cite journal |last1=Aizenman |first1=Elias |last2=Loring |first2=Ralph H. |last3=Reynolds |first3=Ian J. |last4=Rosenberg |first4=Paul A. |date=July 24, 2020 |title=The Redox Biology of Excitotoxic Processes: The NMDA Receptor, TOPA Quinone, and the Oxidative Liberation of Intracellular Zinc |journal=Frontiers in Neuroscience |volume=14 |pages=778 |doi=10.3389/fnins.2020.00778 |doi-access=free |issn=1662-4548 |pmc=7393236 |pmid=32792905}}</ref>