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 alpha, beta or gamma 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.