Excitatory amino acid transporter 1 (EAAT1)

Excitatory amino acid transporter 1 (EAAT1), encoded by the SLC1A3 gene, is a sodium-dependent high-affinity transporter found primarily in astrocytes and Bergmann glia in the brain, with additional expression in the retina and other tissues[1][4][7]. EAAT1’s key function is to remove extracellular glutamate—a principal excitatory neurotransmitter—thereby preventing glutamate-induced neurotoxicity and tightly regulating synaptic signaling[1][4][5]. EAAT1 accomplishes this by symporting glutamate with Na+ and H+, while counter-transporting K+, and also acts as a chloride channel[3][5][7]. Dysfunction or mutation in EAAT1/SLC1A3 is linked to episodic ataxia type 6, several neurodegenerative conditions, and possibly some forms of cancer and osteoarthritis due to impaired glutamate homeostasis[4][2][3]. EAAT1 is a pharmacologically tractable target; competitive (e.g., TBOA) and allosteric (e.g., UCPH101) inhibitors of this transporter have been developed to probe its function and provide leads for selective therapeutic intervention[1][2]. However, therapeutic modulation poses risks of disrupting synaptic and glial homeostasis, with excitotoxicity a major concern if glutamate uptake is excessively reduced[5].

Other names

GLASTGLAST-1Glutamate aspartate transporter 1SLC1A3Sodium-dependent glutamate/aspartate transporter 1Glial high affinity glutamate transporterSolute carrier family 1 member 3

Competitive inhibition (orthosteric inhibition at the substrate site, e.g., TBOA); Allosteric inhibition (e.g., UCPH101 binding locks the transporter in the outward-facing state); Blockade of glutamate reuptake, leading to increased extracellular glutamate