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Regulation of glutamate release from primary afferents and interneurons in the spinal cord by muscarinic receptor subtypes.
J Neurophysiol. 2007 Jan; 97(1):102-9.JN

Abstract

Activation of spinal muscarinic acetylcholine receptors (mAChRs) produces analgesia and inhibits dorsal horn neurons through potentiation of GABAergic/glycinergic tone and inhibition of glutamatergic input. To investigate the mAChR subtypes involved in the inhibitory effect of mAChR agonists on glutamate release, evoked excitatory postsynaptic currents (eEPSCs) were recorded in lamina II neurons using whole cell recordings in rat spinal cord slices. The nonselective mAChR agonist oxotremorine-M concentration-dependently inhibited the monosynaptic and polysynaptic EPSCs elicited by dorsal root stimulation. Interestingly, oxotromorine-M caused a greater inhibition of polysynaptic EPSCs (64.7%) than that of monosynaptic EPSCs (27.9%). In rats pretreated with intrathecal pertussis toxin, oxotremorine-M failed to decrease monosynaptic EPSCs but still partially inhibited the polysynaptic EPSCs in some neurons. This remaining effect was blocked by a relatively selective M(3) antagonist 4-DAMP. Himbacine, an M(2)/M(4) antagonist, or AFDX-116, a selective M(2) antagonist, completely blocked the inhibitory effect of oxotremorine-M on monosynaptic EPSCs. However, the specific M(4) antagonist MT-3 did not alter the effect of oxotremorine-M on monosynaptic EPSCs. Himbacine also partially attenuated the effect of oxotremorine-M on polysynaptic EPSCs in some cells and this effect was abolished by 4-DAMP. Furthermore, oxotremorine-M significantly decreased spontaneous EPSCs in seven of 22 (31.8%) neurons, an effect that was blocked by 4-DAMP. This study provides new information that the M(2) mAChRs play a critical role in the control of glutamatergic input from primary afferents to dorsal horn neurons. The M(3) and M(2)/M(4) subtypes on a subpopulation of interneurons are important for regulation of glutamate release from interneurons in the spinal dorsal horn.

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Authors+Show Affiliations

Zhang HM
Department of Anesthesiology and Pain Medicine, The University of Texas M.D. Anderson Cancer Center, 1400 Holcombe Blvd., Unit 409, Houston, TX 77030, USA.
Chen SR
No affiliation info available
Pan HL
No affiliation info available

MeSH

Afferent PathwaysAnimalsDrug InteractionsExcitatory Postsynaptic PotentialsGlutamic AcidInterneuronsMaleMuscarinic AgonistsMuscarinic AntagonistsNeural InhibitionOrgan Culture TechniquesPosterior Horn CellsPresynaptic TerminalsRatsRats, Sprague-DawleyReceptor, Muscarinic M2Receptor, Muscarinic M3Receptor, Muscarinic M4Receptors, MuscarinicSpinal CordSpinal Nerve RootsSynaptic Transmission

Pub Type(s)

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

Language

eng

PubMed ID

17050831

Citation

Zhang, Hong-Mei, et al. "Regulation of Glutamate Release From Primary Afferents and Interneurons in the Spinal Cord By Muscarinic Receptor Subtypes." Journal of Neurophysiology, vol. 97, no. 1, 2007, pp. 102-9.
Zhang HM, Chen SR, Pan HL. Regulation of glutamate release from primary afferents and interneurons in the spinal cord by muscarinic receptor subtypes. J Neurophysiol. 2007;97(1):102-9.
Zhang, H. M., Chen, S. R., & Pan, H. L. (2007). Regulation of glutamate release from primary afferents and interneurons in the spinal cord by muscarinic receptor subtypes. Journal of Neurophysiology, 97(1), 102-9.
Zhang HM, Chen SR, Pan HL. Regulation of Glutamate Release From Primary Afferents and Interneurons in the Spinal Cord By Muscarinic Receptor Subtypes. J Neurophysiol. 2007;97(1):102-9. PubMed PMID: 17050831.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Regulation of glutamate release from primary afferents and interneurons in the spinal cord by muscarinic receptor subtypes. AU - Zhang,Hong-Mei, AU - Chen,Shao-Rui, AU - Pan,Hui-Lin, Y1 - 2006/10/18/ PY - 2006/10/20/pubmed PY - 2007/3/10/medline PY - 2006/10/20/entrez SP - 102 EP - 9 JF - Journal of neurophysiology JO - J Neurophysiol VL - 97 IS - 1 N2 - Activation of spinal muscarinic acetylcholine receptors (mAChRs) produces analgesia and inhibits dorsal horn neurons through potentiation of GABAergic/glycinergic tone and inhibition of glutamatergic input. To investigate the mAChR subtypes involved in the inhibitory effect of mAChR agonists on glutamate release, evoked excitatory postsynaptic currents (eEPSCs) were recorded in lamina II neurons using whole cell recordings in rat spinal cord slices. The nonselective mAChR agonist oxotremorine-M concentration-dependently inhibited the monosynaptic and polysynaptic EPSCs elicited by dorsal root stimulation. Interestingly, oxotromorine-M caused a greater inhibition of polysynaptic EPSCs (64.7%) than that of monosynaptic EPSCs (27.9%). In rats pretreated with intrathecal pertussis toxin, oxotremorine-M failed to decrease monosynaptic EPSCs but still partially inhibited the polysynaptic EPSCs in some neurons. This remaining effect was blocked by a relatively selective M(3) antagonist 4-DAMP. Himbacine, an M(2)/M(4) antagonist, or AFDX-116, a selective M(2) antagonist, completely blocked the inhibitory effect of oxotremorine-M on monosynaptic EPSCs. However, the specific M(4) antagonist MT-3 did not alter the effect of oxotremorine-M on monosynaptic EPSCs. Himbacine also partially attenuated the effect of oxotremorine-M on polysynaptic EPSCs in some cells and this effect was abolished by 4-DAMP. Furthermore, oxotremorine-M significantly decreased spontaneous EPSCs in seven of 22 (31.8%) neurons, an effect that was blocked by 4-DAMP. This study provides new information that the M(2) mAChRs play a critical role in the control of glutamatergic input from primary afferents to dorsal horn neurons. The M(3) and M(2)/M(4) subtypes on a subpopulation of interneurons are important for regulation of glutamate release from interneurons in the spinal dorsal horn. SN - 0022-3077 UR - https://www.unboundmedicine.com/medline/citation/17050831/Regulation_of_glutamate_release_from_primary_afferents_and_interneurons_in_the_spinal_cord_by_muscarinic_receptor_subtypes_ L2 - https://journals.physiology.org/doi/10.1152/jn.00586.2006?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -