May 2008
Volume 49, Issue 13
ARVO Annual Meeting Abstract  |   May 2008
D-Serine Modulates Glutamatergic Increases of Intracellular Calcium in Rat Retinal Ganglion Cells
Author Affiliations & Notes
  • B. A. Daniels
    Dalhousie University, Halifax, Nova Scotia, Canada
    Anatomy & Neurobiology,
  • J. E. Nason
    Dalhousie University, Halifax, Nova Scotia, Canada
    Anatomy & Neurobiology,
  • W. H. Baldridge
    Dalhousie University, Halifax, Nova Scotia, Canada
    Anatomy & Neurobiology,
    Ophthamology & Visual Sciences,
  • Footnotes
    Commercial Relationships  B.A. Daniels, None; J.E. Nason, None; W.H. Baldridge, None.
  • Footnotes
    Support  CIHR Operating Grant MOP-15683 (WHB), NSERC PGS D3 (BAD) , James Robinson Johnston Scholarship (BAD)
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 5786. doi:
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      B. A. Daniels, J. E. Nason, W. H. Baldridge; D-Serine Modulates Glutamatergic Increases of Intracellular Calcium in Rat Retinal Ganglion Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):5786. doi:

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      © ARVO (1962-2015); The Authors (2016-present)

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Purpose: : It is well documented that glutamatergic activation of NMDA receptors is enhanced by glycine at a separate binding site. Recent studies on retinal ganglion cells (RGCs) have revealed that this co-agonist binding site can also be occupied endogenously by D-serine. Previous work has focused primarily on D-serine modulation of post-synaptic NMDA currents. Given the significant permeability of NMDA channels to calcium we have investigated the effect of D-serine on glutamatergic-induced intracellular calcium [Ca2+]i increases in RGCs in vitro and in situ.

Methods: : Calcium imaging of immunopanned isolated RGCs (P6-8 Long Evans rats) and RGCs in adult whole mount retinas was performed. Isolated RGCs were loaded with fura-2 AM calcium indicator dye and RGCs in the whole mount retinas were loaded with fura dextran. All experiments were performed in Mg2+-free solutions.

Results: : Isolated RGC [Ca2+]i increases produced by application of 10 µM glutamate were enhanced by co-exposure to D-serine in a dose dependant manner. D-Serine concentrations ≥1 µM increased the glutamate-induced [Ca2+]i response (mean ± sd; 1 µM, 118 ± 84% increase; 10 µM, 282 ± 273%; 100 µM, 425 ± 490%). The peak effect of D-serine was seen at 100 µM. At 10 µM, glycine or D-serine enhanced the 10 µM glutamate-induced calcium response to similar levels (379 ± 231% and 474 ± 422%, respectively). This effect was partially blocked by the NMDA co-agonist binding site antagonist 1-aminocyclobutane-1-carboxylic acid (ACBC, 100 µM). In whole mount retinas NMDA-induced (200 µM) [Ca2+]i increases showed no change with the co-application of 100 µM glycine or D-serine. In other experiments endogenous D-serine was degraded by a 10 min exposure to D-amino acid oxidase (400 µg/ml). Subsequent NMDA-induced [Ca2+]i increases were significantly reduced to 65 ± 21% in most RGCs. The calcium response to NMDA was recovered by addition of 500 µM D-serine to 103 ± 35% of the original NMDA-induced response.

Conclusions: : At 10 µM, D-serine and glycine are equally effective as co-agonists of glutamate-induced increases in [Ca2+]i in vitro. In situ, D-serine did not augment the NMDA-induced [Ca2+]i increase possibly due to saturation of the NMDA receptor co-agonist site. Consistent with this hypothesis, enzymatic degradation of D-serine resulted in a reduction of the NMDA-induced [Ca2+]i increase that was recovered by exogenous D-serine application.

Keywords: ganglion cells • calcium • excitatory neurotransmitters 

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