Journal
EUROPEAN JOURNAL OF NEUROSCIENCE
Volume 30, Issue 12, Pages 2308-2317Publisher
WILEY
DOI: 10.1111/j.1460-9568.2009.07020.x
Keywords
coagonist binding sites; GlyT1 glycine transporters; N-methyl-D-aspartic acid receptors; retina
Categories
Funding
- NEI NIH HHS [T32 EY007133, R01 EY003014, R01 EY003014-31] Funding Source: Medline
- NIMH NIH HHS [R01 MH051290] Funding Source: Medline
Ask authors/readers for more resources
We examined the role of GlyT1, the high-affinity glycine transporter, in the mouse retina with an emphasis on the role of glycine as a coagonist of N-methyl-D-aspartic acid (NMDA) receptors. We pursued this objective by studying heterozygote mice deficient in the GlyT1 transporter (GlyT1-/+) and compared those results with wild-type (WT) littermate controls (GlyT1+/+). Capillary electrophoresis was used to separate and quantitatively measure glycine release from isolated retina preparations; pharmacologically blocking GlyT1 with N-[3-([1,1-biphenyl]-4-yloxy)-3-(4-fluorophenyl)propyl]-N-methylglycine in the WT retina generated a significantly larger accumulation of glycine into the bathing environment when compared with the GlyT1-/+ retinas. The relative occupancy state of the NMDA receptor coagonist sites was tested using whole-cell recordings from ganglion cells while bath applying D-serine or D-serine + NMDA. The interpretation of these studies was simplified by blocking post-synaptic inhibition with picrotoxinin and strychnine. NMDA receptor coagonist sites were more saturated and less enhanced by D-serine in the GlyT1-/+ mice compared with the WT controls. Immunoblots of NMDA receptor subunits (NR1, NR2A and NR2B) in WT and GlyT1-/+ animals showed that the NR1 subunits were identical. These observations are discussed in view of contemporary issues about NMDA receptor coagonist function in the vertebrate retina and the role of glycine vs. D-serine as the endogenous coagonist.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available