EXPRESSION OF NON-NMDA GLUTAMATE-RECEPTOR CHANNEL GENES BY CLONAL HUMAN NEURONS

Treatment of the human teratocarcinoma line NTera2/c1.D1 (NT2) with re tinoic acid induces terminal neuronal differentiation. In a previous s tudy, we found that the neurons obtained in this way express functiona l N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptor channels . We now show by reverse transcriptase-polymerase chain reaction and S outhern blotting that these neurons transcribe each of the nine known non-NMDA glutamate receptor genes (GluR1-7, Ka-1, and Ka-2) and that f our of these genes (GluR2, GluR6, GluR7, and Ka-1) are also transcribe d by undifferentiated NT2 cells. Patch clamp studies demonstrate that individual non-NMDA glutamate receptor channels are readily isolated f rom NT2-derived neurons and that these channels are potently modulated by the desensitization blocker cyclothiazide. NT2-derived neurons are susceptible to kainate excitotoxicity but are not injured by prolonge d exposure to ha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate. We ex pect that the NT2-derived human neuronal culture system will facilitat e studies of human neuronal non-NMDA glutamate receptor channels and o f the pathophysiology of neuronal excitotoxicity.