Glutamate receptor ionotropic AMPA subunit 4 (GluA4)

Glutamate receptor ionotropic AMPA subunit 4 (GluA4) is one of four subunits (GluA1–GluA4, encoded by GRIA1–GRIA4) that assemble as tetrameric ligand-gated ion channels, mediating rapid excitatory neurotransmission in the brain. AMPA receptors are key mediators of fast synaptic transmission at glutamatergic synapses and play essential roles in processes such as learning, memory, and plasticity. Most native receptors are heterotetramers, with different subunit combinations giving rise to distinct physiological and pharmacological properties. GluA4 participates in the formation of the cation-selective ion channel pore and determines the receptor’s gating, ion selectivity, and kinetics. Dysfunction or dysregulation of AMPA receptors, including GluA4, is implicated in several neurological and neurodegenerative diseases, making these receptors important therapeutic targets for conditions like epilepsy, ALS, and other CNS disorders. Drugs targeting AMPA receptors can act directly by blocking the ion channel or allosterically modulating the receptor, with effects on neuronal activity, excitotoxicity, and synaptic plasticity.

Other names

GluA4GRIA4 (gene name)GluR4 (older name)AMPA receptor subunit A4Glutamate receptor 4

Competitive antagonism at the glutamate binding site (e.g., NBQX); Noncompetitive antagonism/allosteric inhibition of ion channel function (e.g., perampanel); Blockade of ion channel pore; Modulation of receptor desensitization and synaptic plasticity