Present address: Department of Cell Physiology & Pharmacology, University of Leicester, University Road, Medical Sciences Building, Leicester LE1 9HN, UK.
Active release of glycine or d-serine saturates the glycine site of NMDA receptors at the cerebellar mossy fibre to granule cell synapse
Version of Record online: 9 DEC 2003
European Journal of Neuroscience
Volume 18, Issue 11, pages 2975–2980, December 2003
How to Cite
Billups, D. and Attwell, D. (2003), Active release of glycine or d-serine saturates the glycine site of NMDA receptors at the cerebellar mossy fibre to granule cell synapse. European Journal of Neuroscience, 18: 2975–2980. doi: 10.1111/j.1460-9568.2003.02996.x
- Issue online: 9 DEC 2003
- Version of Record online: 9 DEC 2003
- Received 17 March 2003, revised 1 September 2003, accepted 3 September 2003
- NMDA receptor;
The current and calcium influx generated by NMDA receptors depend on the concentration of the coagonist glycine, or its analogue d-serine, in the synaptic cleft. If there is no release of glycine, the ionic stoichiometry of the glial GlyT1 glycine transporters expressed near NMDA receptors in the brain should be able to lower the extracellular glycine concentration to below the EC50 for coactivation of NMDA receptors. We examined whether changing the glycine or d-serine concentration in the superfusion solution altered the NMDA receptor mediated component of the synaptic current at the rat cerebellar mossy fibre to granule cell synapse. Adding up to 100 µm glycine or d-serine had no effect, implying that the glycine site is saturated. Using the competitive glycine site antagonist 7-chlorokynurenate, and plausible values for the kinetic parameters of NMDA receptors, we estimate that during activation of the mossy fibres the concentration of glycine or d-serine in the synaptic cleft is at least 4.6 µm or 1.5 µm, respectively, requiring active release of glycine or d-serine.