EAAT1EAAT5

EAAT1–EAAT5 are excitatory amino acid transporters belonging to the SLC1 family. They comprise five closely related transporters encoded by SLC1A3 (EAAT1), SLC1A2 (EAAT2), SLC1A1 (EAAT3), SLC1A6 (EAAT4) and SLC1A7 (EAAT5). They mediate the uptake of glutamate, and to a lesser extent aspartate, from the extracellular space in the central nervous system and retina, thereby terminating excitatory signaling and maintaining low ambient levels of these amino acids.

Distribution and specialization: EAAT2 is highly expressed in astrocytes throughout the CNS and accounts for the majority of glutamate clearance; EAAT1 is also glial and co-distributed with EAAT2. EAAT3 is primarily neuronal and contributes to synaptic and extrasynaptic uptake; EAAT4 is enriched in cerebellar Purkinje cells; EAAT5 is concentrated in the retina, particularly in photoreceptor and bipolar cell layers, where it participates in fast glutamate clearance and an associated chloride conductance.

Function and mechanism: The transporters are high-affinity, Na+-dependent solute carriers that co-transport Na+ and H+ with glutamate and counter-transport K+. They reduce extracellular glutamate to prevent excitotoxicity. In addition to transport, several EAATs provide an anion conductance that can influence membrane excitability, with EAAT5 exhibiting notable chloride conductance in the retina. Structural work supports a trimeric organization with an elevator-like substrate translocation mechanism; activity is regulated by trafficking to and from the plasma membrane and by neuronal activity, inflammation, and injury.

Clinical relevance: Dysregulation of EAAT function is linked to several neurological disorders, including stroke, epilepsy and neurodegenerative diseases. Upregulation of EAAT2 (SLC1A2) in astrocytes is pursued as a therapeutic strategy in conditions such as ALS. Pharmacological agents exist that inhibit or enhance transporter function and expression (for example, broad-spectrum EAAT inhibitors and compounds that increase EAAT2 expression, such as ceftriaxone in experimental settings).