Ionotropic AMPA-type glutamate receptor (AMPA receptor (AMPAR))

The Ionotropic AMPA-type glutamate receptor is a ligand-gated ion channel predominantly responsible for fast excitatory neurotransmission in the mammalian central nervous system. Activated by the neurotransmitter glutamate, these receptors mediate the majority of rapid synaptic responses by allowing cation influx, primarily sodium and to a lesser extent calcium, thus depolarizing neurons. Structurally, AMPA receptors are tetramers formed by combinations of four subunits (GluA1–GluA4, encoded by GRIA1–GRIA4), often modulated by auxiliary proteins such as TARPs and cornichon homologs, which alter channel kinetics and trafficking. AMPA receptors play crucial roles in synaptic plasticity, learning, and memory; their dysfunction or overactivation is linked to neurological diseases such as epilepsy, neurodegeneration, and ischemia. They are the target of several clinical drugs (e.g., perampanel for epilepsy) as well as research compounds that act as antagonists or modulators of glutamatergic signaling.

Other names

AMPA receptorAMPARα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptorGluA receptorGluR (obsolete, now generally replaced by GluA nomenclature for subunits)

Antagonists inhibit AMPA receptor-mediated synaptic transmission by blocking glutamate binding or channel opening (e.g., perampanel, talampanel, NBQX) Positive allosteric modulators (ampakines) increase channel opening probability or slow desensitization, enhancing synaptic transmission Negative allosteric modulators reduce channel function by destabilizing the open state or accelerating desensitization