alpha-Aminoadipic acid blocks the Na(+)-dependent glutamate transport into acutely isolated Müller glial cells from guinea pig retina.
The effect of the glial toxin alpha-aminoadipic acid (AAA) upon the Na+/glutamate cotransporter of acutely isolated guinea pig retinal glial cells was studied using the whole-cell voltage-clamp technique. Glutamate evoked an inward 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 extracellular Na+ or intracellular K+ was removed. The glutamate uptake blocker, PDC (200 microM), 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 Km of 499 microM at a glutamate concentration of 10 microM. 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.
Pannicke
T
T
Carl-Ludwig-Institute of Physiology, University of Leipzig, Germany.
Stabel
J
J
Heinemann
U
U
Reichelt
W
W
D015074:2-Aminoadipic Acid / Q000494:pharmacology*; D027322:Amino Acid Transport System X-AG; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002352:Carrier Proteins / Q000378:metabolism; D003998:Dicarboxylic Acids / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D050491:Glutamate Plasma Membrane Transport Proteins; D018698:Glutamic Acid / Q000378:metabolism* / Q000494:pharmacology; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism; D011759:Pyrrolidines / Q000494:pharmacology; D012160:Retina / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012964:Sodium / Q000502:physiology*; D027981:Symporters
D027322:Amino Acid Transport System X-AG; D002352:Carrier Proteins; D003998:Dicarboxylic Acids; D018691:Excitatory Amino Acid Antagonists; D050491:Glutamate Plasma Membrane Transport Proteins; D015221:Potassium Channels; D011759:Pyrrolidines; D027981:Symporters; D015074:2-Aminoadipic Acid; D001464:Barium; D018698:Glutamic Acid; C083486:pyrrolidine-2,4-dicarboxylic acid; D012964:Sodium