ionotropic glutamate receptor

{{Short description|Ligand-gated ion channels}}

{{Infobox protein family

| Symbol = Lig_chan

| Name = Lig_chan

| image = PDB 1s50 EBI.jpg

| width =

| caption = x-ray structure of the glur6 ligand binding core (s1s2a) in complex with glutamate at 1.65 a resolution

| Pfam = PF00060

| Pfam_clan = CL0030

| InterPro = IPR001320

| SMART =

| PROSITE =

| MEROPS =

| SCOP = 1gr2

| TCDB = 1.A.10

| OPM family = 8

| OPM protein = 3kg2

| CAZy =

| CDD =

}}

Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that are activated by the neurotransmitter glutamate.{{cite journal |vauthors=Traynelis SF, Wollmuth LP, McBain CJ, Menniti FS, Vance KM, Ogden KK, Hansen KB, Yuan H, Myers SJ, Dingledine R | title = Glutamate receptor ion channels: structure, regulation, and function | journal = Pharmacol. Rev. | volume = 62 | issue = 3 | pages = 405–496 | date = September 2010 | pmid = 20716669 | doi = 10.1124/pr.109.002451 | pmc=2964903}} They mediate the majority of excitatory synaptic transmission throughout the central nervous system and are key players in synaptic plasticity, which is important for learning and memory. iGluRs have been divided into four subtypes on the basis of their ligand binding properties (pharmacology) and sequence similarity: AMPA receptors, kainate receptors, NMDA receptors and delta receptors (see below).{{cite journal | vauthors = Collingridge GL, Olsen RW, Peters J, Spedding M | title = A nomenclature for ligand-gated ion channels | journal = Neuropharmacology | volume = 56 | issue = 1 | pages = 2–5 | date = January 2009 | pmid = 18655795 | doi = 10.1016/j.neuropharm.2008.06.063 | pmc=2847504}}

AMPA receptors are the main charge carriers during basal transmission, permitting influx of sodium ions to depolarise the postsynaptic membrane. NMDA receptors are blocked by magnesium ions and therefore only permit ion flux following prior depolarisation. This enables them to act as coincidence detectors for synaptic plasticity. Calcium influx through NMDA receptors leads to persistent modifications in the strength of synaptic transmission.{{cite journal |vauthors=Bliss TV, Collingridge GL | title = A synaptic model of memory: long-term potentiation in the hippocampus | journal = Nature | volume = 361 | issue = 6407 | pages = 31–39 | date = January 1993 | pmid = 8421494 | doi = 10.1038/361031a0 | bibcode = 1993Natur.361...31B | s2cid = 4326182 }}{{cite journal | vauthors = Citri A, Malenka RC | title = Synaptic plasticity: multiple forms, functions, and mechanisms | journal = Neuropsychopharmacology | volume = 33 | issue = 1 | pages = 18–41 | date = January 2008 | pmid = 17728696 | doi = 10.1038/sj.npp.1301559 | doi-access = free }}

iGluRs are tetramers (they are formed of four subunits). All subunits have a shared architecture with four domain layers: two extracellular clamshell domains called the N-terminal domain (NTD) and ligand-binding domain (LBD; which binds glutamate), the transmembrane domain (TMD) that forms the ion channel, and an intracellular C-terminal domain (CTD).{{cite journal |vauthors=Traynelis SF, Wollmuth LP, McBain CJ, Menniti FS, Vance KM, Ogden KK, Hansen KB, Yuan H, Myers SJ, Dingledine R | title = Glutamate receptor ion channels: structure, regulation, and function | journal = Pharmacol. Rev. | volume = 62 | issue = 3 | pages = 405–496 | date = September 2010 | pmid = 20716669 | doi = 10.1124/pr.109.002451 | pmc=2964903}}