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Dynamic regulation of glycinergic input to spinal dorsal horn neurones by muscarinic receptor subtypes in rats.
J Physiol. 2006 Mar 01; 571(Pt 2):403-13.JP

Abstract

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 microm 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.

Authors+Show Affiliations

Department of Anesthesiology, Pennsylvania State University College of Medicine, Hershey 17033, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

16410279

Citation

Wang, Xiu-Li, et al. "Dynamic Regulation of Glycinergic Input to Spinal Dorsal Horn Neurones By Muscarinic Receptor Subtypes in Rats." The Journal of Physiology, vol. 571, no. Pt 2, 2006, pp. 403-13.
Wang XL, Zhang HM, Li DP, et al. Dynamic regulation of glycinergic input to spinal dorsal horn neurones by muscarinic receptor subtypes in rats. J Physiol. 2006;571(Pt 2):403-13.
Wang, X. L., Zhang, H. M., Li, D. P., Chen, S. R., & Pan, H. L. (2006). Dynamic regulation of glycinergic input to spinal dorsal horn neurones by muscarinic receptor subtypes in rats. The Journal of Physiology, 571(Pt 2), 403-13.
Wang XL, et al. Dynamic Regulation of Glycinergic Input to Spinal Dorsal Horn Neurones By Muscarinic Receptor Subtypes in Rats. J Physiol. 2006 Mar 1;571(Pt 2):403-13. PubMed PMID: 16410279.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dynamic regulation of glycinergic input to spinal dorsal horn neurones by muscarinic receptor subtypes in rats. AU - Wang,Xiu-Li, AU - Zhang,Hong-Mei, AU - Li,De-Pei, AU - Chen,Shao-Rui, AU - Pan,Hui-Lin, Y1 - 2006/01/12/ PY - 2006/1/18/pubmed PY - 2006/7/13/medline PY - 2006/1/18/entrez SP - 403 EP - 13 JF - The Journal of physiology JO - J Physiol VL - 571 IS - Pt 2 N2 - 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 microm 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. SN - 0022-3751 UR - https://www.unboundmedicine.com/medline/citation/16410279/Dynamic_regulation_of_glycinergic_input_to_spinal_dorsal_horn_neurones_by_muscarinic_receptor_subtypes_in_rats_ L2 - https://doi.org/10.1113/jphysiol.2005.102905 DB - PRIME DP - Unbound Medicine ER -