High abundance of GluR1 mRNA and reduced Q/R editing of GluR2 mRNA in individual NADPH-diaphorase neurons.
Kim, DY; Kim, SH; Choi, HB; Min, C; Gwag, BJ
Molecular and cellular neurosciences, 17(6):1025-1033, 2001
Molecular and cellular neurosciences
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-sensitive glutamate receptors. This has been attributed to Ca2+ entry through AMPA/kainate receptors in NADPH-d(+) neurons. In this study, we applied single cell RT-PCR technique to test the hypothesis that differences in levels and processing of the GluR2 subunit would contribute to the selective vulnerability of NADPH-d(+) neurons to AMPA. The nested PCR specific for GluR1-GluR4 showed that rat striatal NADPH-d(+) neurons expressed twice as much GluR1 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 and the reduced ratio of GluR2/GluR1 render NADPH-d(+) neurons highly sensitive to Ca2+-mediated AMPA neurotoxicity. In support of this, most NADPH-d(+) neurons exposed to 100 microM AMPA showed Co2+ uptake and survived AMPA challenge only in the absence of extracellular Ca2+.
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