Facilitation of spinal NMDA receptor currents by spillover of synaptically released glycine.
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 of inflammatory hyperalgesia.
Ahmadi
Seifollah
S
Institut für Experimentelle und Klinische Pharmakologie und Toxikologie, Universität Erlangen-Nürnberg, Fahrstrasse 17, D-91054 Erlangen, Germany.
Muth-Selbach
Uta
U
Lauterbach
Andreas
A
Lipfert
Peter
P
Neuhuber
Winfried L
WL
Zeilhofer
Hanns Ulrich
HU
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D000870:Anterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D004058:Diffusion; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D005998:Glycine / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D007395:Interneurons / Q000378:metabolism; D009433:Neural Inhibition / Q000187:drug effects; D018847:Opioid Peptides / Q000494:pharmacology; D010147:Pain Measurement; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D012694:Serine / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism; D013569:Synapses / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D013696:Temperature
D000700:Analgesics; D018847:Opioid Peptides; D016194:Receptors, N-Methyl-D-Aspartate; C111148:nocistatin; D012694:Serine; D005998:Glycine