Ionotropic glutamate receptor explained

Symbol:Lig_chan
Lig_chan
Pfam:PF00060
Pfam Clan:CL0030
Interpro:IPR001320
Scop:1gr2
Tcdb:1.A.10
Opm Family:8
Opm Protein:3kg2

Ionotropic glutamate receptors (iGluRs) are ligand-gated ion channels that are activated by the neurotransmitter glutamate.[1] 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).[2]

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.[3] [4]

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).[5]

Human proteins/genes encoding iGluR subunits

AMPA receptors

GluA1/GRIA1; GluA2/GRIA2; GluA3/GRIA3; GluA4/GRIA4;

delta receptors: GluD1/GRID1; GluD2/GRID2;

kainate receptors: GluK1/GRIK1; GluK2/GRIK2; GluK3/GRIK3; GluK4/GRIK4; GluK5/GRIK5;

NMDA receptors

GluN1/GRIN1; GluN2A/GRIN2A; GluN2B/GRIN2B; GluN2C/GRIN2C; GluN2D/GRIN2D; GluN3A/GRIN3A; GluN3B/GRIN3B;

Notes and References

  1. Traynelis SF, Wollmuth LP, McBain CJ, Menniti FS, Vance KM, Ogden KK, Hansen KB, Yuan H, Myers SJ, Dingledine R . Glutamate receptor ion channels: structure, regulation, and function . Pharmacol. Rev. . 62 . 3 . 405–496 . September 2010 . 20716669 . 10.1124/pr.109.002451 . 2964903.
  2. Collingridge GL, Olsen RW, Peters J, Spedding M . A nomenclature for ligand-gated ion channels . Neuropharmacology . 56 . 1 . 2–5 . January 2009 . 18655795 . 10.1016/j.neuropharm.2008.06.063 . 2847504.
  3. Bliss TV, Collingridge GL . A synaptic model of memory: long-term potentiation in the hippocampus . Nature . 361 . 6407 . 31–39 . January 1993 . 8421494 . 10.1038/361031a0 . 1993Natur.361...31B . 4326182 .
  4. Citri A, Malenka RC . Synaptic plasticity: multiple forms, functions, and mechanisms . Neuropsychopharmacology . 33 . 1 . 18–41 . January 2008 . 17728696 . 10.1038/sj.npp.1301559 . free .
  5. Traynelis SF, Wollmuth LP, McBain CJ, Menniti FS, Vance KM, Ogden KK, Hansen KB, Yuan H, Myers SJ, Dingledine R . Glutamate receptor ion channels: structure, regulation, and function . Pharmacol. Rev. . 62 . 3 . 405–496 . September 2010 . 20716669 . 10.1124/pr.109.002451 . 2964903.