Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid and kainate-type glutamate receptor (AMPAR/KAR)

Alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and kainate-type glutamate receptors, collectively known as non-NMDA receptors, are ionotropic receptors that mediate the majority of fast excitatory synaptic transmission in the central nervous system [1, 2]. These receptors are tetrameric assemblies of subunits—GluA1-4 for AMPA receptors and GluK1-5 for kainate receptors—that form ligand-gated ion channels [1, 4]. Upon binding the endogenous neurotransmitter glutamate, the channel opens to allow the influx of cations, primarily sodium and sometimes calcium, leading to rapid depolarization of the postsynaptic membrane [1, 3]. They are essential for synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), which are the cellular foundations of learning and memory [1, 2]. Dysregulation of these receptors is linked to a variety of neurological conditions, including epilepsy, stroke-induced excitotoxicity, and neurodegenerative diseases like Alzheimer's and ALS [1, 5]. Pharmacological agents targeting these receptors include antagonists like perampanel, used for seizure management, and positive allosteric modulators (ampakines) being investigated for cognitive enhancement [2, 5].

Other names

Non-NMDA glutamate receptorNon-NMDA receptorQuisqualate receptoriGluR (non-NMDA)

Negative allosteric modulation (non-competitive antagonism) and competitive antagonism to inhibit ion channel opening; positive allosteric modulation to enhance receptor activity by slowing desensitization.