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This Article Full Text Full Text (PDF) All Versions of this Article: 571/2/403    most recent jphysiol.2005.102905v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Wang, X.-L. Articles by Pan, H.-L. Search for Related Content PubMed PubMed Citation Articles by Wang, X.-L. Articles by Pan, H.-L. Related Collections Neuroscience

¹ Department of Anesthesiology, Department of Neural and Behavioral Sciences, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA
² Department of Anesthesiology, The Third Hospital of HeBei Medical University, Shijiazhuang 050051, China

Activation of spinal muscarinic acetylcholine receptors (mAChRs) inhibits nociception. However, the cellular mechanisms of this action are not fully known. In this study, we determined the role of mAChR subtypes in regulation of synaptic glycine release in the spinal cord. Whole-cell voltage-clamp recordings were performed on lamina II neurones in the rat spinal cord slices. The mAChR agonist oxotremorine-M significantly increased the frequency of glycinergic sIPSCs but not mIPSCs. Surprisingly, the effect of oxotremorine-M on sIPSCs was largely attenuated at a higher concentration. On the other hand, 1–10 µM oxotremorine-M dose-dependently increased the frequency of sIPSCs in rats pretreated with intrathecal pertussis toxin. Furthermore, oxotremorine-M also dose-dependently increased the frequency of sIPSCs in the presence of himbacine (an M₂/M₄ mAChR antagonist) or AF-DX116 (an M₂ mAChR antagonist). The M₃ mAChR antagonist 4-DAMP abolished the stimulatory effect of oxotremorine-M on sIPSCs. Interestingly, the GABA_B receptor antagonist CGP55845 potentiated the stimulatory effect of oxotremorine-M on sIPSCs. In the presence of CGP55845, both himbacine and AF-DX116 similarly reduced the potentiating effect of oxotremorine-M on sIPSCs. Collectively, these data suggest that the M₃ subtype is present on the somatodendritic site of glycinergic neurones and is mainly responsible for muscarinic potentiation of glycinergic input to spinal dorsal horn neurones. Concurrent stimulation of mAChRs on adjacent GABAergic interneurones attenuates synaptic glycine release through presynaptic GABA_B receptors on glycinergic interneurones. This study illustrates a complex dynamic interaction between GABAergic and glycinergic synapses in the spinal cord dorsal horn.

(Received 2 December 2005; accepted after revision 11 January 2006; first published online 12 January 2006)
Corresponding author H.-L. Pan: Department of Anesthesiology and Pain Medicine, University of Texas, M.D. Anderson Cancer Center, Unit 409, 1400 Holcombe Blvd, Houston, TX77030, USA. Email: hpan{at}psu.edu

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