Reduction of GluR2 RNA editing, a molecular change that increases calcium influx through AMPA receptors, selective in the spinal ventral gray of patients with amyotrophic lateral sclerosis.

Enhancement of calcium influx through the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)/kainate receptor is a plausible mechanism underlying selective neuronal death in amyotrophic lateral sclerosis (ALS). The calcium conductance of the AMPA receptor is regulated by the GluR2 subunit that is edited at the glutamine/arginine residue site in the subunit assembly. We investigated the molecular changes of GluR2 mRNA in the spinal cord of ALS cases, those of cases with other neurological diseases, and those of normal cases using reverse transcription-polymerase chain reaction combined with restriction enzyme cleavage. We found that the editing efficiency was significantly lower only in the ventral gray of ALS cases (virtually 0% in 2 cases) than in any spinal region of the disease controls and normal controls. In addition, expression of GluR2 mRNA is lower in the ventral gray of the ALS cases and disease controls than in that of the normal controls. The above molecular changes of GluR2 mRNA in the ventral gray of ALS cases may enhance calcium influx through AMPA receptors, thereby promoting neuronal vulnerability. The decrement of GluR2 mRNA editing efficiency is unique to the ventral gray of ALS cases and may be closely linked to the etiology of ALS.