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Glycine Binding Sites of Presynaptic NMDA Receptors May Tonically Regulate Glutamate Release in the Rat Visual Cortex

Department of Physiology, School of Medicine, Xi'an Jiaotong University, Zhuque Dajie 205, Xi'an, Shannxi, People's Republic of China

Submitted 13 September 2006; accepted in final form 4 November 2006

In the CNS, activation of N-methyl-D-aspartate receptor (NMDA-R) glycine binding sites is a prerequisite for activation of postsynaptic NMDA-Rs by the excitatory neurotransmitter glutamate. Here we provide electrophysiological evidence that the glycine binding sites of presynaptic NMDA-Rs regulate glutamate release in layer II/III pyramidal neurons of the rat visual cortex. Specifically, our results reveal that the frequency of miniature excitatory postsynaptic currents is significantly reduced by 7-chloro-kynurenic acid (7-Cl KYNA), a NMDA-R glycine binding site antagonist, and glycine or D-serine reverses this effect. Similar results are obtained when the open-channel NMDA receptor blocker, MK-801, is included in the recording pipette. Our data indicate that the glycine binding site of postsynaptic NMDA-Rs is not saturated. Moreover, they suggest that presynaptic NMDA-Rs are located in layer II/III pyramidal neurons of the rat visual cortex and that the glycine binding site of presynaptic NMDA-Rs tonically regulates glutamate release.

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