Up‐regulated GLT‐1 Resists Glutamate Toxicity and Attenuates Glutamate‐induced Calcium Loading in Cultured Neurocytes

Glutamate transporter‐1 (GLT‐1) plays a dual role in glutamate transportation: both normally devotion to the clearance of glutamate and during some pathological conditions extruding glutamate to the extracellular space. Therefore, it is uncertain whether increased expression of GLT‐1 will actually be helpful against glutamate excitotoxicity. In this study, GLT‐1 up‐regulation was induced by ceftriaxone, and L‐glutamate was added to induce glutamate toxicity in primary cultured rat cortical cells. The results showed that up‐regulated GLT‐1 induced by 1 μM ceftriaxone for 2 days markedly increased cell viability, decreased apoptotic cell death and alleviated ultrastructural damage induced by 50 μM glutamate 15 min. as well as promoted L‐[³H]‐glutamate uptake in cultured cells. GLT‐1 up‐regulation had no effect on the intracellular free calcium concentration ([Ca²⁺]_i) in the resting situation, while relieved intracellular calcium overloading by reducing the elevation and promoting the recovery of [Ca²⁺]_i following stimulation of 50 μM glutamate for 2 min. Applying 100 μM dihydrokainic acid (GLT‐1 antagonist) 30 sec. before glutamate eliminated the above effect of GLT‐1 up‐regulation on [Ca²⁺]_i. In conclusion, GLT‐1 up‐regulation induced by ceftriaxone plays a positive glutamate transporting role against glutamate toxicity in primary cultured rat cortical cells.