EAAT1EAAT2

EAAT1 and EAAT2 are two related glutamate transporters in the central nervous system that play a key role in clearing the neurotransmitter glutamate from the synaptic cleft. They belong to the SLC1 family of amino acid transporters and are encoded by the genes SLC1A3 (EAAT1, also called GLAST) and SLC1A2 (EAAT2, also called GLT-1). Both are high-affinity, sodium-dependent transporters expressed primarily by astrocytes, though their regional distribution varies in the brain.

EAAT1 is found predominantly in astrocytes throughout the brain with substantial expression in the cerebellum. EAAT2 is the principal glutamate transporter in the forebrain and spinal cord and accounts for the majority of extracellular glutamate uptake in these regions. Together, they regulate extracellular glutamate levels, terminate synaptic transmission, and help prevent excitotoxic neuronal injury.

Mechanistically, EAAT1 and EAAT2 operate by co-transporting glutamate with sodium and a proton into the cell while counter-transporting potassium out of the cell. In addition to their transport function, they exhibit an associated anion conductance that is activated upon substrate binding. This combination supports rapid clearance of glutamate and helps maintain ion homeostasis in the extracellular space.

Clinical and research relevance includes the role of transporter dysfunction in neurodegenerative and psychiatric disorders. Reduced EAAT2 (GLT-1) activity is linked to excitotoxic vulnerability in conditions such as ALS, cortical ischemia, and epilepsy. Therapeutic strategies aiming to upregulate EAAT2 expression or function, including certain pharmacological agents, are under investigation to enhance glutamate uptake and confer neuroprotection.