Glutamate receptor ionotropic AMPA type subunit 2 (GluA2)

Glutamate receptor ionotropic AMPA type subunit 2 (GluA2) is a critical component of the AMPA-type glutamate receptors, which are ligand-gated ion channels mediating the majority of fast excitatory neurotransmission in the central nervous system[1][3][4]. GluA2, encoded by the GRIA2 gene, is a member of the ionotropic glutamate receptor family, assembling as a tetramer with other AMPA subunits (GluA1-4). The presence of GluA2 in the receptor complex determines calcium ion permeability; RNA editing at a specific site in GluA2 changes a single amino acid, thereby rendering the channel impermeable to Ca²⁺—a property essential for protecting neurons from excitotoxicity[1][3]. This subunit plays an essential regulatory role in synaptic transmission, plasticity, and neuronal survival. Dysfunction or altered expression of GluA2 has been implicated in various neurological and psychiatric disorders, including ALS, epilepsy, ischemia, and certain neurodevelopmental syndromes[1][3]. AMPA receptors, including those containing GluA2, are targets for both marketed antiepileptic drugs (e.g., perampanel) and numerous experimental compounds[3]. Safety concerns for drugs targeting this receptor include cognitive impairment and the risk of seizures or excitotoxic neuronal damage, especially if the Ca²⁺-impermeability conferred by edited GluA2 is compromised[1][3].

Other names

GluA2GluR2Glutamate receptor 2AMPA receptor subunit GluA2GRIA2 (gene name)

Antagonists block glutamate binding or channel opening, inhibiting excitatory neurotransmission Positive allosteric modulators enhance channel opening or reduce desensitization, increasing excitatory neurotransmission