L-Glutamate, the major excitatory neurotransmitter in the central nervous system, operates through several receptors that are categorized as ionotropic (ligand-gated cation channels) or metabotropic (G-protein coupled receptors).

The ligand-gated ion channel family consists of 15 members that have been subdivided into three families based on their pharmacological profile: the a-amino-3-hydroxy-5-methyl-4-isoazolepropionic acid (AMPA) preferring receptors, the N-methyl-D-aspartate (NMDA) preferring and the kainate preferring receptors.

The AMPA receptor subfamily includes four members AMPA1 to AMPA4, also known as GluR1 to GluR4 respectively.

The functional AMPA channel is believed to be a tetramer, with most neuronal AMPA receptors being heterotetramers composed of AMPA1 plus AMPA2 or AMPA2 plus AMPA3 channels, although homotetramers can also been found.

AMPA receptors are permeable to cations Na⁺, K⁺ and Ca²⁺. The Ca²⁺ permeability is dependent on the presence of AMPA2: whenever this subunit is present, the channel will be impermeable to Ca²⁺.¹

Gating of AMPA receptors by glutamate is extremely fast and therefore the AMPA receptors mediate most excitatory (depolarizing) currents in the brain during basal neuronal activity. The depolarization caused by the activation of post-synaptic AMPA receptors is necessary for the activation of NMDA receptors that will open only in the presence of both glutamate and a depolarized membrane potential.

Synaptic strength that is defined as the level of post-synaptic depolarization can be long term (hence the term long term potentiation, LTP) and therefore induce changes in signaling and protein synthesis in the activated neuron. These changes are associated with memory formation and learning. Changes in synaptic strength are thought to involve rapid movement of the AMPA receptors in and out of the synapses and a great deal of effort has focused in understanding the mechanisms that govern AMPA receptor trafficking.²

The exact physiological role of the AMPA3 receptor is not clear but a role in the modulation of oscillatory networks affecting sleep and breathing has been suggested.³