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The Journal of Neuroscience, January 1, 2000, 20(1):123-132

AMPA Receptor Calcium Permeability, GluR2 Expression, and Selective Motoneuron Vulnerability

Wim Vandenberghe^{1, 2}, Wim Robberecht², and James R. Brorson¹

¹  Department of Neurology, The University of Chicago, Chicago, Illinois 60637, and ² Department of Neurology, University of Leuven, 3000 Leuven, Belgium

AMPA receptor-mediated excitotoxicity is proposed to play a major pathogenic role in the selective motoneuron death of amyotrophic lateral sclerosis. Motoneurons have been shown in various models to be more susceptible to AMPA receptor-mediated injury than other spinal neurons. It has been hypothesized that this selective vulnerability of motoneurons is caused by the expression of highly Ca²⁺-permeable AMPA receptors and a complete or relative lack of the AMPA receptor subunit Glu receptor 2 (GluR2). The aim of this study was to quantify the relative Ca²⁺ permeability of AMPA receptors and the fractional expression of GluR2 in motoneurons by combining whole-cell patch-clamp electrophysiology and single-cell RT-PCR and to compare these properties with those of dorsal horn neurons. Spinal motoneurons and dorsal horn neurons were isolated from embryonic rats and cultured on spinal astrocytes. As in previous studies, motoneurons were significantly more vulnerable to AMPA and kainate than dorsal horn neurons. However, all motoneurons expressed GluR2 mRNA (~40% of total AMPA receptor subunit mRNA), and their AMPA receptors had intermediate whole-cell relative Ca²⁺ permeability (P_Ca²⁺/P_Cs⁺ ~ 0.4). AMPA receptor P_Ca²⁺/P_Cs⁺ and the relative abundance of GluR2 varied more widely in dorsal horn neurons than in motoneurons, but the mean values did not differ significantly between the two cell populations. GluR2 was virtually completely edited at the Q/R site both in motoneurons and dorsal horn neurons. These results indicate that the selective vulnerability of motoneurons to AMPA receptor agonists is not determined solely by whole-cell relative Ca²⁺ permeability of AMPA receptors.

Key words: amyotrophic lateral sclerosis; excitotoxicity; kainate; dorsal horn; rat; culture

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Copyright © 2000 Society for Neuroscience  0270-6474/0/201123-10$05.00/0

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