Glutamate Transporters/Na(+), K(+)-ATPase Involving in the Neuroprotective Effect as a Potential Regulatory Target of Glutamate Uptake.

The glutamate (Glu) transporters GLAST and GLT-1, as the two most important transporters in brain tissue, transport Glu from the extracellular space into the cell protecting against Glu toxicity. Furthermore, GLAST and GLT-1 are sodium-dependent Glu transporters (GluTs) that rely on sodium and potassium gradients generated principally by Na(+), K(+)-ATPase to generate ion gradients that drive Glu uptake. There is an interaction between Na(+), K(+)-ATPase and GluTs to modulate Glu uptake, and Na(+), K(+)-ATPase α, β or γ subunit can be directly coupled to GluTs, co-localizing with GLAST or GLT-1 in vivo to form a macromolecular complex and operate as a functional unit to regulate glutamatergic neurotransmission. Therefore, GluTs/Na(+), K(+)-ATPase may be involved in the neuroprotective effect as a potential regulatory target of Glu uptake in neurodegenerative diseases induced by Glu-mediated neurotoxicity as the final common pathway.