ALPHA-AMINOADIPIC ACID BLOCKS THE NA-DEPENDENT GLUTAMATE TRANSPORT INTO ACUTELY ISOLATED MULLER GLIAL-CELLS FROM GUINEA-PIG RETINA()

The effect of the glial toxin alpha-aminoadipic acid (AAA) upon the Na +/glutamatecotransporter of acutely isolated guinea pig retinal glial cells was studied using the whole-cell voltage-clamp technique. Glutam ate evoked an inward current in these cells at negative holding potent ials dependent on the presence of extracellular Na+ and intracellular K+. A reversal potential could not be found for the current. L-trans-P yrrolidine-2.4-dicarboxylic acid (PDC), a blocker of Na+-dependent glu tamate uptake, diminished the glutamate current also in our cells. App lication of L-AAA. also generated an inward current at negative holdin g potentials, without a reversal potential, being suppressed if extrac ellular Na+ or intracellular K+ was removed. The glutamate uptake bloc ker, PDC (200 mu M), blocked the L-AAA (1 mM) current. Thus, L-AAA pro ved to be transported by the Na+/glutamate transporter of Muller cells . Hence, glutamate currents were diminished by L-AAA competitively wit h a K-m of 499 mu M at a glutamate concentration of 10 mu M. The Na+/g lutamate uptake was less sensitive to DL- and D-AAA block. It is sugge sted that the blocking effect of AAA on Na+-dependent glutamate uptake into glial cells might be involved in the well known glia toxicity of this compound.