Glutamate receptor ionotropic, AMPA type subunit 4 (GRIA4)

Glutamate receptor ionotropic, AMPA type subunit 4 (GRIA4) is a critical component of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor complex, which mediates fast excitatory synaptic transmission in the central nervous system (UniProt P48058; NCBI Gene 2893). As a ligand-gated ion channel, it functions as a heterotetrameric assembly with other subunits (GluA1-3) to facilitate the influx of cations, primarily sodium and potassium, upon glutamate binding (UniProt P48058). GRIA4 plays a significant role in synaptic plasticity, particularly during early development and in specific brain regions like the thalamus and cerebellum (NCBI Gene 2893; PMID: 27535537). Dysregulation or genetic mutations in the GRIA4 gene are associated with various neurological conditions, including epilepsy, intellectual disability, and schizophrenia (PMID: 27535537; PMID: 31110191). Pharmacologically, AMPA receptors containing the GRIA4 subunit are targeted by non-competitive antagonists such as perampanel for the treatment of seizures (DrugBank DB08883). Additionally, positive allosteric modulators are being explored for their potential to enhance cognitive function in neurodegenerative and psychiatric disorders (PMID: 21414448).

Other names

GluA4GluR4GluR-DAMPA-selective glutamate receptor 4Glutamate receptor 4

Non-competitive antagonism of the AMPA-type glutamate receptor, leading to reduced excitatory neurotransmission; also targeted by positive allosteric modulators (AMPAkines) to enhance synaptic signaling.