There are many evidences implicating glutamatergic toxicity as a contributory factor in the selective neuronal injury occurring in amyotrophic lateral sclerosis (ALS). This neurodegenerative disorder is characterized by the progressive loss of motor neurons, whose pathogenesis is thought to involve Ca2+ influx mediated by α-amino-3-hydroxy-5-methyl-isoxazole-4- propionate receptors (AMPARs). In the present study we report alterations in the AMPARs function in a transgenic mouse-model of the human SOD1 G93A familial ALS. Compared with those expressed in motor neurons carrying the human wild type gene, AMPAR-gated channels expressed in motor neurons carrying the human mutant gene exhibited modified permeability, altered agonist cooperativity between the sites involved in the process of channel opening and were responsible for slower spontaneous synaptic events. These observations demonstrate that the SOD1G93A mutation induces changes in AMPAR functions which may underlie the increased vulnerability of motor neurons to glutamatergic excitotoxicity in ALS.
|Number of pages||12|
|Publication status||Published - Nov 20 2003|
- Glutamate receptors
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