Ionotropic glutamate receptor (AMPA and Kainate types) (iGluR (AMPA/KAR))

Ionotropic glutamate receptors of the AMPA and Kainate types are ligand-gated ion channels that mediate the majority of fast excitatory synaptic transmission in the central nervous system (Traynelis et al., 2010). AMPA receptors (AMPARs) are primarily responsible for the rapid depolarization of the postsynaptic membrane, while Kainate receptors (KARs) play specialized roles in modulating synaptic transmission and network excitability (IUPHAR/BPS Guide to Pharmacology). These receptors are tetrameric assemblies of subunits—GluA1-4 for AMPARs and GluK1-5 for KARs—which determine their specific kinetic properties and ion selectivity, including calcium permeability (UniProt). Dysregulation of these receptors is a hallmark of various neurological disorders; for instance, excessive activation can lead to excitotoxic cell death in stroke and amyotrophic lateral sclerosis (ALS) (StatPearls). Pharmacologically, AMPA receptor antagonists like perampanel are clinically used as anticonvulsants to treat epilepsy (FDA). Research into positive allosteric modulators, known as AMPAkines, aims to enhance cognitive function in conditions like Alzheimer's disease and schizophrenia (PubMed). Overall, these receptors are critical for synaptic plasticity, learning, and memory, making them high-value targets for CNS drug development.

Other names

Non-NMDA receptorsAMPA receptorsKainate receptorsGluA receptorsGluK receptorsQuisqualate receptors (obsolete for AMPA)

Antagonism of the ion channel to inhibit cation influx (Na+, K+, Ca2+), thereby reducing excitatory neurotransmission.