Taurine potentiates presynaptic NMDA receptors in hippocampal Schaffer collateral axons

We have previously shown that activation of presynaptic N-methyl-(D)-aspartate (NMDA) receptors (NMDAR) enhances the amplitude of the presynaptic fibre volley (FV) evoked in Schaffer collateral axons of rat hippocampal slices, by a mechanism independent of extracellular Ca2+. Here we compared the pharmacological characteristics of presynaptic NMDARs affecting axon excitability (activated by 10-300 mu(M) NMDA for 10 min), with those mediating field excitatory postsynaptic potentials (NMDA-fEPSP). We found that NMDA-induced potentiation was completely inhibited by NVP-AAM077, an antagonist of NR2A-containing NMDAR, but not by ifenprodil, an NR2B-selective antagonist. The inhibitor of the glycine-binding site in NMDARs, 7-clorokynurenic acid (7-CK), was more potent against NMDA-fEPSP (IC50 = 6.3 +/- 1.3 mu(M)) than against the NMDA-induced FV potentiation (IC50 = 26.5 +/- 1.3 mu(M)). Moreover, both post- and presynaptic NMDAR-mediated phenomena were enhanced by glycine and (D)-serine, but taurine, an endogenous analogue of glycine, only enhanced the latter (EC50 = 19 mu(M)). Taurine was able to block the inhibitory effect of low doses of 7-CK on NMDA-induced FV potentiation, while glycine and (D)-serine only reduced the effects of higher concentrations of this drug. Surprisingly, the enhancing effect of taurine on NMDA-induced FV potentiation was blocked when it was co-applied with glycine. Furthermore, the glutamate released synaptically with a train of stimuli also increased FV amplitude by a mechanism dependent on NMDARs; this was potentiated by taurine but not by co-application of taurine and glycine. These results reveal that presynaptic NMDARs have unique properties that mediate the facilitation of axon excitability.