Ionotropic glutamate receptor AMPA-type subunits (AMPAR)

Ionotropic glutamate receptor AMPA-type subunits (GluA1-4) are the primary mediators of fast excitatory synaptic transmission in the mammalian central nervous system [1.2.1, 1.4.4]. These receptors are tetrameric assemblies of four subunits that form a ligand-gated ion channel, which opens in response to the binding of the neurotransmitter glutamate to allow the influx of cations like sodium and calcium [1.2.1, 1.5.1]. AMPA receptors play a critical role in synaptic plasticity, including long-term potentiation (LTP) and long-term depression (LTD), which are the cellular foundations of learning and memory [1.1.3, 1.2.2]. Dysregulation of AMPA receptor function is implicated in a wide range of neurological and psychiatric disorders, including epilepsy, Alzheimer's disease, and amyotrophic lateral sclerosis (ALS) [1.2.1, 1.5.2]. Pharmacological targeting of these receptors includes non-competitive antagonists like perampanel for seizure control and positive allosteric modulators (ampakines) being investigated for cognitive enhancement [1.3.3, 1.5.3]. However, therapeutic use is often limited by safety concerns such as sedation, ataxia, and potential for excitotoxicity or proconvulsive effects [1.5.3, 1.5.4]. The subunit composition, particularly the presence of the edited GluA2 subunit, determines the calcium permeability and overall signaling properties of the receptor complex [1.2.4, 1.4.4]. Recent research also highlights their role in conditions like long COVID-associated brain fog and chronic pain [1.1.1, 1.1.4].

Other names

AMPA receptorAlpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptorGluR1-4GluA1-4GRIA1-4Quisqualate receptor

Non-competitive antagonism, competitive antagonism, positive allosteric modulation, and negative allosteric modulation of the ion channel pore or ligand-binding domain.