T. Pannicke et al., ALPHA-AMINOADIPIC ACID BLOCKS THE NA-DEPENDENT GLUTAMATE TRANSPORT INTO ACUTELY ISOLATED MULLER GLIAL-CELLS FROM GUINEA-PIG RETINA(), Pflugers Archiv, 429(1), 1994, pp. 140-142
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.