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Science 27 June 2003:
Vol. 300. no. 5628, pp. 2094 - 2097
DOI: 10.1126/science.1083970
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Reports

Facilitation of Spinal NMDA Receptor Currents by Spillover of Synaptically Released Glycine

Seifollah Ahmadi,1* Uta Muth-Selbach,2* Andreas Lauterbach,1* Peter Lipfert,2 Winfried L. Neuhuber,3 Hanns Ulrich Zeilhofer1{dagger}

In the mammalian CNS, N-methyl-D-aspartate (NMDA) receptors serve prominent roles in many physiological and pathophysiological processes including pain transmission. For full activation, NMDA receptors require the binding of glycine. It is not known whether the brain uses changes in extracellular glycine to modulate synaptic NMDA responses. Here, we show that synaptically released glycine facilitates NMDA receptor currents in the superficial dorsal horn, an area critically involved in pain processing. During high presynaptic activity, glycine released from inhibitory interneurons escapes the synaptic cleft and reaches nearby NMDA receptors by so-called spillover. In vivo, this process may contribute to the development ofinflammatory hyperalgesia.

1 Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität Erlangen-Nürnberg, Fahrstrasse 17, D-91054 Erlangen, Germany.
2 Klinik für Anästhesiologie, Moorenstrasse 5, Universitätsklinikum Düsseldorf, D-40225 Düsseldorf, Germany.
3 Institut für Anatomie, Krankenhausstrasse 9, Universität Erlangen-Nürnberg, D-91054 Erlangen, Germany.



* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: zeilhofer{at}pharmakologie.uni-erlangen.de

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