Glutamate in Neurodegenerative Disorders: Phenotype Resulting from Decreased Expression of AMPA Receptor GIuR-B Subunit mRNA in Rats
The excitatory neurotransmitter glutamate activates various classes of ionotropic receptors in the mammalian central nervous system. αAmino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) and kainate (KA) receptor stimulation triggers Na+ influx into neurons, while N-methyl-D-aspartate (NMDA) receptor stimulation additionally leads to considerable Ca2+ influx (Hollmann and Heinemann 1994). Relative impermeability of the AMPA receptor channel to Ca2+ is regulated by the Q/R locus within the channel pore on the M2 region of the G1uR-B subunit. Expression of either glutamine (Q) or arginine (R) within this locus is controlled by posttranscriptional RNA editing (Sommer et al. 1991). Transgenic mice engineered to synthesize unedited GluR-B subunits express Ca2+permeable AMPA receptors. These mice develop progressive neurodegeneration and spontaneous seizures (Brusa et al. 1995).
KeywordsPermeability Cage Arginine Glutamine NMDA
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