Glutamate ionotropic receptor AMPA type subunit 2-containing receptor complex (GluA2-containing AMPAR)

The GluA2-containing AMPA receptor is a subtype of ionotropic glutamate receptor that mediates the majority of fast excitatory synaptic transmission in the central nervous system [Traynelis et al., 2010, Pharm Rev]. The inclusion of the GluA2 subunit, particularly in its Q/R edited form, is a primary determinant of the receptor's biophysical properties, rendering the channel impermeable to calcium ions and protecting neurons from excitotoxicity [Isaac et al., 2007, Neuron]. Transmembrane AMPA receptor regulatory proteins (TARPs), specifically TARP γ-2 (also known as Stargazin), act as essential auxiliary subunits that regulate the trafficking of these receptors to the postsynaptic membrane and modulate their gating kinetics [Jackson & Nicoll, 2011, Neuron]. Dysregulation of GluA2-containing receptors is implicated in various neurological disorders, including epilepsy, amyotrophic lateral sclerosis (ALS), and neurodegenerative diseases like Alzheimer's [Kwak & Weiss, 2006, Neurobiol Dis; Guntupalli et al., 2016, Mol Brain]. Pharmacological targeting of these receptors often involves non-competitive antagonists or allosteric modulators, with some newer compounds specifically targeting the interaction between the receptor and its TARP subunits to achieve regional or functional selectivity [Kato et al., 2016, Nature Medicine]. Understanding the stoichiometry and auxiliary protein associations of these receptors is crucial for developing therapies that balance efficacy with minimized side effects such as sedation or motor impairment [French et al., 2012, Neurology].

Other names

GRIA2-containing AMPA receptorGluR2-containing AMPA receptorStargazin-associated AMPA receptorGluA2/TARP γ-2 complexAMPA receptor subunit 2 complex

Non-competitive antagonism of the AMPA receptor [French et al., 2012, Neurology]; TARP-dependent negative allosteric modulation [Kato et al., 2016, Nature Medicine]; Positive allosteric modulation [Lynch, 2006, Ampakines].