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The glial glutamate aspartate transporter, commonly known as excitatory amino acid transporter 1 (EAAT1) or GLAST (SLC1A3), is a sodium-dependent transporter predominantly expressed in glial cells, including astrocytes and Bergmann glia in the cerebellum. It plays a critical role in clearing glutamate from the synaptic cleft and extrasynaptic spaces by facilitating reuptake into glia, thereby maintaining low extracellular glutamate levels to prevent excitotoxicity and regulate glutamatergic signaling. EAAT1 co-transports glutamate with 2-3 Na+ ions and 1 H+, counter-transports 1 K+, and functions as a trimer where each monomer can independently transport substrate. Once internalized, glutamate is converted to glutamine via glutamine synthetase in astrocytes, supporting the glutamate-glutamine cycle that recycles the neurotransmitter back to neurons. Dysregulation of EAAT1 contributes to glutamatergic dysfunction implicated in neurodegenerative diseases and psychiatric disorders, with altered expression, trafficking, and glycosylation affecting its activity. While no approved drugs directly target EAAT1, inhibitors like TBOA are used in research to study transport mechanisms.
Competitive inhibition of glutamate uptake, Na+-dependent transport blockade
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