December 2002
Volume 43, Issue 13
Free
ARVO Annual Meeting Abstract  |   December 2002
D-Serine Acts as a Co-Agonist at NMDA Receptors in the Vertebrate Retina
Author Affiliations & Notes
  • ER Stevens
    Neuroscience University of Minnesota Minneapolis MN
  • TA Doerr
    Neuroscience University of Minnesota Minneapolis MN
  • P Kim
    Neuroscience Johns Hopkins University Baltimore MD
  • RF Miller
    Neuroscience University of Minnesota Minneapolis MN
  • SH Snyder
    Neuroscience Johns Hopkins University Baltimore MD
  • Footnotes
    Commercial Relationships   E.R. Stevens, None; T.A. Doerr, None; P. Kim, None; R.F. Miller, None; S.H. Snyder, None. Grant Identification: NIH Grants EY03014 & EY12833
Investigative Ophthalmology & Visual Science December 2002, Vol.43, 4764. doi:
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    • Get Citation

      ER Stevens, TA Doerr, P Kim, RF Miller, SH Snyder; D-Serine Acts as a Co-Agonist at NMDA Receptors in the Vertebrate Retina . Invest. Ophthalmol. Vis. Sci. 2002;43(13):4764.

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Abstract

Abstract: : Purpose: To determine if D-serine is present in the vertebrate retina, and to assess its role in shaping ganglion cell light responses. Methods: Immunohistochemical studies were performed on amphibian retinas (Necturus maculosus and Ambystoma tigrum) to establish the location of D-serine and serine racemase, the enzyme which synthesizes D-serine. In addition, the role of D-serine was evaluated using whole-cell recordings from ganglion cells in an isolated, perfused tiger salamander retina. Results: D-serine and serine racemase are present in the inner layers of the amphibian retina. Co-labeling with glutamine synthetase, a glial enzyme, shows significant overlap, localizing serine racemase in Muller cells. D-serine appears to be synthesized and stored in close proximity to NMDA receptors in the inner retina. Whole-cell recordings from ganglion cells in the tiger salmander retina demonstrate that exogenously applied D-Serine potentiates tonic inward currents and enhances the light-evoked amplitude and duration of ON and OFF responses in ganglion cells in Mg-free Ringer using holding potentials between -60 mV and -70 mV. The effects of D-serine are reversible, and blocked by the NMDA receptor antagonist, D-AP7. The potentiation by D-serine was also blocked by 7-chloro-kynurenic acid (7ClKyn), a competitive antagonist at the strychnine-insensitive, glycine binding site of the NMDA receptor. This block by 7ClKyn could be overcome by the application of additional D-serine, strongly suggesting that D-serine interacts with the glycine binding site of the NMDA receptor. Conclusion: The present studies suggest that D-serine is synthesized in Muller cell processes in the inner retinal layers adjacent to its putative site of action on the NMDA receptors of ganglion and amacrine cells. D-serine appears to act as a co-agonist at the glycine binding site of NMDA receptors and to potentiate the light-evoked activity of ganglion cells. These results also strongly suggest that the glycine binding site of the NMDA receptors is not normally saturated, indicating a role for D-serine in modulating the light-evoked activity of ganglion cells through control of NMDA receptors. This pathway demonstrates a new mechanism through which Muller cells have some control of ganglion cell excitablility.

Keywords: 401 excitatory amino acid receptors • 541 receptors: pharmacology/physiology • 415 ganglion cells 
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