High abundance of GluR1 mRNA and reduced Q/R editing of GluR2 mRNA in individual NADPH-diaphorase neurons

Striatal and cortical neurons containing NADPH-diaphorase [NADPH-d(+)] are highly vulnerable to excitotoxicity that is induced by activation of alpha -amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)- or kainate-sens itive glutamate receptors. This has been attributed to Ca2+ entry through A MPA/kainate receptors in NADPHd(+) neurons. In this study, we applied singl e cell RT-PCR technique to test the hypothesis that differences in levels a nd processing of the GluR2 subunit would contribute to the selective vulner ability of NADPH-d(+) neurons to AMPA. The nested PCR specific for GluR1-Gl uR4 showed that rat striatal NADPH-d(+) neurons expressed twice as much Glu R1 mRNA as NADPH-d(-) neurons did. The percentage of RNA editing at the Q/R site of GluR2 was 46% in NADPH-d(+) neurons and 92% in NADPH-d(-) neurons. These results suggest that the unedited expression of GluR2 end the reduce d ratio of GluR2/GluR1 render NADPH-d(+) neurons highly sensitive to Ca2+-m ediated AMPA neurotoxicity. In support of this, most NADPH-d(+) neurons exp osed to 100 muM AMPA showed Co2+ uptake and survived AMPA challenge only in the absence of extracellular Ca2+.