PURPOSE. Functional N-methyl-D- aspartate ( NMDA) receptors (NMDARs) in Muller glia may influence glutamate neurotransmission through feedback loops between glia and neurons. The physiologic properties of NMDARs derive from the subunit composition of the tetrameric receptor. We characterized glycine binding to the NMDAR coagonist site in Muller cell membranes and determined NMDAR subunit expression in chick Muller glia compared with retinal neurons to make predictions about the heteromeric assembly of NMDARs.METHODS. Kinetic and pharmacologic properties of the glycine coagonist site were determined by radiolabeled ligand binding to membrane preparations from chick Muller glia and retinal neurons in primary culture. The molecular composition of NMDARs was analyzed by RT-PCR amplification and Western blotting.RESULTS. The NMDAR coagonist site in Muller cell membranes has 5-fold lower affinity for glycine and 30-fold lower affinity for D-serine compared with values obtained for synaptic membranes from whole retina and with reported values in brain tissue. NR1 subunit N-terminal and C-terminal splice-variant expression also differs in Muller cells and retinal neurons.CONCLUSIONS. Pharmacologic characteristics of NMDAR coagonist-site differ in Muller glia and neurons from the retina, in agreement with the distinct subunit expression profile found. Whereas NMDARs in Muller glia contain exclusively exon 5 that lacks NR1 subunits, receptors in distinct subtypes of neurons may contain NR1 with or without exon 5, suggesting a cell-specific assembly of the NMDAR complex. Structural differences in NMDARs could underlie the differential participation of neurons and glia in the physiologic control of glutamate transmission in the retina.
Última actualización: 24/10/2016