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Dynamic control of glutamatergic synaptic input in the spinal cord by muscarinic receptor subtypes defined using knockout mice.
J Biol Chem. 2010 Dec 24; 285(52):40427-37.JB

Abstract

Activation of muscarinic acetylcholine receptors (mAChRs) in the spinal cord inhibits pain transmission. At least three mAChR subtypes (M(2), M(3), and M(4)) are present in the spinal dorsal horn. However, it is not clear how each mAChR subtype contributes to the regulation of glutamatergic input to dorsal horn neurons. We recorded spontaneous excitatory postsynaptic currents (sEPSCs) from lamina II neurons in spinal cord slices from wild-type (WT) and mAChR subtype knock-out (KO) mice. The mAChR agonist oxotremorine-M increased the frequency of glutamatergic sEPSCs in 68.2% neurons from WT mice and decreased the sEPSC frequency in 21.2% neurons. Oxotremorine-M also increased the sEPSC frequency in ∼50% neurons from M(3)-single KO and M(1)/M(3) double-KO mice. In addition, the M(3) antagonist J104129 did not block the stimulatory effect of oxotremorine-M in the majority of neurons from WT mice. Strikingly, in M(5)-single KO mice, oxotremorine-M increased sEPSCs in only 26.3% neurons, and J104129 abolished this effect. In M(2)/M(4) double-KO mice, but not M(2)- or M(4)-single KO mice, oxotremorine-M inhibited sEPSCs in significantly fewer neurons compared with WT mice, and blocking group II/III metabotropic glutamate receptors abolished this effect. The M(2)/M(4) antagonist himbacine either attenuated the inhibitory effect of oxotremorine-M or potentiated the stimulatory effect of oxotremorine-M in WT mice. Our study demonstrates that activation of the M(2) and M(4) receptor subtypes inhibits synaptic glutamate release to dorsal horn neurons. M(5) is the predominant receptor subtype that potentiates glutamatergic synaptic transmission in the spinal cord.

Authors+Show Affiliations

Department of Anesthesiology and Perioperative Medicine, The University of Texas, M. D. Anderson Cancer Center, Houston, Texas 77030, 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
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20940295

Citation

Chen, Shao-Rui, et al. "Dynamic Control of Glutamatergic Synaptic Input in the Spinal Cord By Muscarinic Receptor Subtypes Defined Using Knockout Mice." The Journal of Biological Chemistry, vol. 285, no. 52, 2010, pp. 40427-37.
Chen SR, Chen H, Yuan WX, et al. Dynamic control of glutamatergic synaptic input in the spinal cord by muscarinic receptor subtypes defined using knockout mice. J Biol Chem. 2010;285(52):40427-37.
Chen, S. R., Chen, H., Yuan, W. X., Wess, J., & Pan, H. L. (2010). Dynamic control of glutamatergic synaptic input in the spinal cord by muscarinic receptor subtypes defined using knockout mice. The Journal of Biological Chemistry, 285(52), 40427-37. https://doi.org/10.1074/jbc.M110.176966
Chen SR, et al. Dynamic Control of Glutamatergic Synaptic Input in the Spinal Cord By Muscarinic Receptor Subtypes Defined Using Knockout Mice. J Biol Chem. 2010 Dec 24;285(52):40427-37. PubMed PMID: 20940295.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dynamic control of glutamatergic synaptic input in the spinal cord by muscarinic receptor subtypes defined using knockout mice. AU - Chen,Shao-Rui, AU - Chen,Hong, AU - Yuan,Wei-Xiu, AU - Wess,Jürgen, AU - Pan,Hui-Lin, Y1 - 2010/10/12/ PY - 2010/10/14/entrez PY - 2010/10/14/pubmed PY - 2011/1/25/medline SP - 40427 EP - 37 JF - The Journal of biological chemistry JO - J Biol Chem VL - 285 IS - 52 N2 - Activation of muscarinic acetylcholine receptors (mAChRs) in the spinal cord inhibits pain transmission. At least three mAChR subtypes (M(2), M(3), and M(4)) are present in the spinal dorsal horn. However, it is not clear how each mAChR subtype contributes to the regulation of glutamatergic input to dorsal horn neurons. We recorded spontaneous excitatory postsynaptic currents (sEPSCs) from lamina II neurons in spinal cord slices from wild-type (WT) and mAChR subtype knock-out (KO) mice. The mAChR agonist oxotremorine-M increased the frequency of glutamatergic sEPSCs in 68.2% neurons from WT mice and decreased the sEPSC frequency in 21.2% neurons. Oxotremorine-M also increased the sEPSC frequency in ∼50% neurons from M(3)-single KO and M(1)/M(3) double-KO mice. In addition, the M(3) antagonist J104129 did not block the stimulatory effect of oxotremorine-M in the majority of neurons from WT mice. Strikingly, in M(5)-single KO mice, oxotremorine-M increased sEPSCs in only 26.3% neurons, and J104129 abolished this effect. In M(2)/M(4) double-KO mice, but not M(2)- or M(4)-single KO mice, oxotremorine-M inhibited sEPSCs in significantly fewer neurons compared with WT mice, and blocking group II/III metabotropic glutamate receptors abolished this effect. The M(2)/M(4) antagonist himbacine either attenuated the inhibitory effect of oxotremorine-M or potentiated the stimulatory effect of oxotremorine-M in WT mice. Our study demonstrates that activation of the M(2) and M(4) receptor subtypes inhibits synaptic glutamate release to dorsal horn neurons. M(5) is the predominant receptor subtype that potentiates glutamatergic synaptic transmission in the spinal cord. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/20940295/Dynamic_control_of_glutamatergic_synaptic_input_in_the_spinal_cord_by_muscarinic_receptor_subtypes_defined_using_knockout_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(19)76209-7 DB - PRIME DP - Unbound Medicine ER -