Alpha-aminoadipic acid blocks the Na⁺-dependent glutamate transport into acutely isolated Müller glial cells from guinea pig retina

Abstract

The effect of the glial toxin α-aminoadipic acid (AAA) upon theNa⁺/glutamate cotransporter of acutely isolated guinea pig retinal glial cells was studied using the whole-cell voltage-clamp technique. Glutamate evoked an in ward current in these cells at negative holding potentials dependent on the presence of extracellular Na⁺ and intracellular K⁺. A reversal potential could not be found for the current. L-trans-Pyrrolidine-2.4-dicarboxylic acid (PDC), a blocker of Na⁺-dependent glutamate uptake, diminished the glutamate current also in our cells. Application of L-AAA also generated an inward current at negative holding potentials, without a reversal potential, being suppressed if extracellularNa⁺ or intracellular K⁺ was removed. The glutamate uptake blocker, PDC (200 μM), blocked the L-AAA (1 mM) current. Thus, L-AAA proved to be transported by the Na⁺/glutamate transporter of Müller cells. Hence, glutamate currents were diminished by L-AAA competitively with a K_m of 499 μM at a glutamate concentration of 10 μM. The Na⁺/glutamate uptake was less sensitive to DL- and D-AAA block. It is suggested 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.