Glutamate receptor ion channels: structure, regulation, and function.
The mammalian ionotropic glutamate receptor family encodes 18 gene products that coassemble to form ligand-gated ion channels containing an agonist recognition site, a transmembrane ion permeation pathway, and gating elements that couple agonist-induced conformational changes to the opening or closing of the permeation pore. Glutamate receptors mediate fast excitatory synaptic transmission in the central nervous system and are localized on neuronal and non-neuronal cells. These receptors regulate a broad spectrum of processes in the brain, spinal cord, retina, and peripheral nervous system. Glutamate receptors are postulated to play important roles in numerous neurological diseases and have attracted intense scrutiny. The description of glutamate receptor structure, including its transmembrane elements, reveals a complex assembly of multiple semiautonomous extracellular domains linked to a pore-forming element with striking resemblance to an inverted potassium channel. In this review we discuss International Union of Basic and Clinical Pharmacology glutamate receptor nomenclature, structure, assembly, accessory subunits, interacting proteins, gene expression and translation, post-translational modifications, agonist and antagonist pharmacology, allosteric modulation, mechanisms of gating and permeation, roles in normal physiological function, as well as the potential therapeutic use of pharmacological agents acting at glutamate receptors.
Traynelis
Stephen F
SF
Department of Pharmacology, Emory University School of Medicine, Rollins Research Center, 1510 Clifton Road, Atlanta, GA 30322-3090, USA. strayne@emory.edu
Wollmuth
Lonnie P
LP
McBain
Chris J
CJ
Menniti
Frank S
FS
Vance
Katie M
KM
Ogden
Kevin K
KK
Hansen
Kasper B
KB
Yuan
Hongjie
H
Myers
Scott J
SJ
Dingledine
Ray
R
D015870:Gene Expression; D006801:Humans; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011499:Protein Processing, Post-Translational; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D017470:Receptors, Glutamate / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009435:Synaptic Transmission; D009626:Terminology as Topic
D007473:Ion Channels; D021122:Protein Subunits; D017470:Receptors, Glutamate