Editing NMDA receptor (section)

==Receptor modulation==
The NMDA receptor is a non-specific cation channel that can allow the passage of Ca<sup>2+</sup> and Na<sup>+</sup> into the cell and K<sup>+</sup> out of the cell. The [[excitatory postsynaptic potential]] (EPSP) produced by activation of an NMDA receptor increases the concentration of Ca<sup>2+</sup> in the cell. The Ca<sup>2+</sup> can in turn function as a [[second messenger]] in various [[signaling pathway]]s. However, the NMDA receptor cation channel is blocked by Mg<sup>2+</sup> at resting membrane potential.<ref name="Purves129-131">{{cite book | vauthors = Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia AS, McNamara JD, White LE |title=Neuroscience | edition = 4th |publisher=Sinauer Associates |pages=129–131 |year=2008 |isbn=978-0-87893-697-7 |url=http://www.sinauer.com/neuroscience4e |url-status=dead |archive-url=https://web.archive.org/web/20110927082419/http://www.sinauer.com/neuroscience4e/ |archive-date=2011-09-27 }}</ref> Magnesium unblock is not instantaneous; to unblock all available channels, the postsynaptic cell must be depolarized for a sufficiently long period of time (in the scale of milliseconds).<ref name=Vargas-Caballero>{{cite journal | vauthors = Vargas-Caballero M, Robinson HP | title = Fast and slow voltage-dependent dynamics of magnesium block in the NMDA receptor: the asymmetric trapping block model | journal = The Journal of Neuroscience | volume = 24 | issue = 27 | pages = 6171–6180 | date = July 2004 | pmid = 15240809 | pmc = 6729657 | doi = 10.1523/jneurosci.1380-04.2004 }}</ref>

Therefore, the NMDA receptor functions as a "molecular [[Coincidence detection in neurobiology|coincidence detector]]". Its ion channel opens only when the following two conditions are met: glutamate is bound to the receptor, and the postsynaptic cell is depolarized (which removes the Mg<sup>2+</sup> blocking the channel). This property of the NMDA receptor explains many aspects of [[long-term potentiation]] (LTP) and [[synaptic plasticity]].<ref name="Purves191-195">{{cite book | vauthors = Purves D, Augustine GJ, Fitzpatrick D, Hall WC, LaMantia AS, McNamara JD, White LE  |title=Neuroscience | edition = 4th |publisher=Sinauer Associates |pages=191–195 |year=2008 |isbn=978-0-87893-697-7 |url=http://www.sinauer.com/neuroscience4e |url-status=dead |archive-url=https://web.archive.org/web/20110927082419/http://www.sinauer.com/neuroscience4e/ |archive-date=2011-09-27 }}</ref>

In a [[Resting membrane potential|resting-membrane potential]], the NMDA receptor pore is opened allowing for an influx of external magnesium ions binding to prevent further ion permeation.<ref>{{cite journal | vauthors = Nowak L, Bregestovski P, Ascher P, Herbet A, Prochiantz A | title = Magnesium gates glutamate-activated channels in mouse central neurones | journal = Nature | volume = 307 | issue = 5950 | pages = 462–465 | date = February 1984 | pmid = 6320006 | doi = 10.1038/307462a0 | bibcode = 1984Natur.307..462N | s2cid = 4344173 }}</ref> External magnesium ions are in a [[millimolar]] range while intracellular magnesium ions are at a [[micromolar]] range to result in negative membrane potential. NMDA receptors are modulated by a number of [[endogenous]] and [[exogenous]] compounds and play a key role in a wide range of [[physiology|physiological]] (e.g., [[memory]]) and [[pathology|pathological]] processes (e.g., [[excitotoxicity]]). Magnesium works to potentiate NMDA-induced responses at positive membrane potentials while blocking the NMDA channel. The use of calcium, potassium, and sodium are used to modulate the activity of NMDARs passing through the NMDA membrane. Changes in H<sup>+</sup> concentration can partially inhibit the activity of NMDA receptors in different physiological conditions.