Glutamate receptor ionotropic, AMPA type subunit 3 (GRIA3)

Glutamate receptor ionotropic, AMPA type subunit 3 (GRIA3), also known as GluA3, is a critical component of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, which are the primary mediators of fast excitatory synaptic transmission in the mammalian central nervous system [1, 9]. These receptors function as ligand-gated ion channels that open in response to glutamate binding, allowing the influx of cations like sodium and calcium to depolarize the postsynaptic membrane [9, 21]. GRIA3 plays a vital role in synaptic plasticity, long-term potentiation, and the regulation of neural network excitability, particularly in the hippocampus and thalamus [6, 15]. Mutations in the GRIA3 gene are linked to various neurodevelopmental disorders, including X-linked intellectual disability (Wu type) and early infantile epileptic encephalopathy, with phenotypes often depending on whether the variant causes a gain or loss of receptor function [11, 13]. Therapeutically, AMPA receptors containing the GluA3 subunit are targeted by the non-competitive antagonist perampanel for the treatment of epilepsy [21, 25]. Additionally, positive allosteric modulators, such as ampakines, are being explored for their potential to enhance cognitive function in conditions like schizophrenia and Alzheimer's disease [22, 24].

Other names

GluA3GluR3GluR-CGLUR3GLURCMRX94MRXSWGlutamate receptor 3Glutamate ionotropic receptor AMPA type subunit 3iGluR3

Non-competitive antagonism of the AMPA receptor, positive allosteric modulation, and stabilization of the open-channel state.