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Cholinergic modulation of primary afferent glutamatergic transmission in rat medullary dorsal horn neurons.
Neuropharmacology. 2013 Dec; 75:295-303.N

Abstract

Although muscarinic acetylcholine (mACh) receptors are expressed in trigeminal ganglia, it is still unknown whether mACh receptors modulate glutamatergic transmission from primary afferents onto medullary dorsal horn neurons. In this study, we have addressed the cholinergic modulation of primary afferent glutamatergic transmission using a conventional whole cell patch clamp technique. Glutamatergic excitatory postsynaptic currents (EPSCs) were evoked from primary afferents by electrical stimulation of trigeminal tract and monosynaptic EPSCs were recorded from medullary dorsal horn neurons of rat horizontal brain stem slices. Muscarine and ACh reversibly and concentration-dependently decreased the amplitude of glutamatergic EPSCs and increased the paired-pulse ratio. In addition, muscarine reduced the frequency of miniature EPSCs without affecting the current amplitude, suggesting that muscarine acts presynaptically to decrease the probability of glutamate release onto medullary dorsal horn neurons. The muscarine-induced decrease of glutamatergic EPSCs was significantly occluded by methoctramine or AF-DX116, M2 receptor antagonists, but not pirenzepine, J104129 and MT-3, selective M1, M3 and M4 receptor antagonists. The muscarine-induced decrease of glutamatergic EPSCs was highly dependent on the extracellular Ca2+ concentration. Physostigmine and clinically available acetylcholinesterase inhibitors, such as rivastigmine and donepezil, significantly shifted the concentration-inhibition relationship of ACh for glutamatergic EPSCs. These results suggest that muscarine acts on presynaptic M2 receptors to inhibit glutamatergic transmission by reducing the Ca2+ influx into primary afferent terminals, and that M2 receptor agonists and acetylcholinesterase inhibitors could be, at least, potential targets to reduce nociceptive transmission from orofacial tissues.

Authors+Show Affiliations

Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea.Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea.Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea.Department of Pharmacology, School of Dentistry, Kyungpook National University, Daegu, Republic of Korea; Brain Science & Engineering Institute, Kyungpook National University, Daegu 700-412, Republic of Korea. Electronic address: jis7619@mail.knu.ac.kr.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23954675

Citation

Jeong, Seok-Gwon, et al. "Cholinergic Modulation of Primary Afferent Glutamatergic Transmission in Rat Medullary Dorsal Horn Neurons." Neuropharmacology, vol. 75, 2013, pp. 295-303.
Jeong SG, Choi IS, Cho JH, et al. Cholinergic modulation of primary afferent glutamatergic transmission in rat medullary dorsal horn neurons. Neuropharmacology. 2013;75:295-303.
Jeong, S. G., Choi, I. S., Cho, J. H., & Jang, I. S. (2013). Cholinergic modulation of primary afferent glutamatergic transmission in rat medullary dorsal horn neurons. Neuropharmacology, 75, 295-303. https://doi.org/10.1016/j.neuropharm.2013.07.030
Jeong SG, et al. Cholinergic Modulation of Primary Afferent Glutamatergic Transmission in Rat Medullary Dorsal Horn Neurons. Neuropharmacology. 2013;75:295-303. PubMed PMID: 23954675.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cholinergic modulation of primary afferent glutamatergic transmission in rat medullary dorsal horn neurons. AU - Jeong,Seok-Gwon, AU - Choi,In-Sun, AU - Cho,Jin-Hwa, AU - Jang,Il-Sung, Y1 - 2013/08/13/ PY - 2013/04/24/received PY - 2013/06/28/revised PY - 2013/07/22/accepted PY - 2013/8/20/entrez PY - 2013/8/21/pubmed PY - 2014/8/20/medline KW - (R)-(+)-[2,3-dihydro-5-methyl-3-(4-morpholinylmethyl)pyrrolo[1,2,3-de]-1,4-benzoxazin-6-yl]-1-naphthalenylmethanone mesylate KW - (αR)-α-cyclopentyl-α-hydroxy-N-[1-(4-methyl-3-pentenyl)-4-piperidinyl]benzeneacetamide fumarate KW - 1-(2,4-dichlorophenyl)-5-(4-iodophenyl)-4-methyl-N-4-morpholinyl-1H-pyrazole-3-carboxamide KW - 11-[[2-[(diethylamino)methyl]-1-piperidinyl]acetyl]-5,11-dihydro-6H-pyrido[2,3-b][1,4]benzodiazepin-6-one KW - 6-cyano-7-nitroquinoxaline-2,3-dione KW - 6-imino-3-(4-methoxyphenyl)-1(6H)-pyridazinebutanoic acid HBr KW - ACSF KW - ACh KW - AChE KW - AF-DX116 KW - AM281 KW - APV KW - CNQX KW - DL-2-amino-5-phosphonovaleric acid KW - DRG KW - EPSCs KW - J104129 KW - Kolmogorov–Smirnov KW - K–S KW - Medullary dorsal horn KW - PPR KW - Pain KW - Patch clamp KW - Presynaptic mACh receptors KW - SEM KW - SR95531 KW - TG KW - TTX KW - VDCCs KW - Win 55,212-2 KW - [Ca(2+)](o) KW - acetylcholine KW - acetylcholinesterase KW - artificial cerebrospinal fluid KW - dorsal root ganglion KW - excitatory postsynaptic currents KW - extracellular Ca(2+) concentration KW - mACh KW - mEPSCs KW - miniature excitatory postsynaptic currents KW - muscarinic acetylcholine KW - paired-pulse ratio KW - standard error of the mean KW - tetrodotoxin KW - trigeminal ganglion KW - voltage-dependent Ca(2+) channels SP - 295 EP - 303 JF - Neuropharmacology JO - Neuropharmacology VL - 75 N2 - Although muscarinic acetylcholine (mACh) receptors are expressed in trigeminal ganglia, it is still unknown whether mACh receptors modulate glutamatergic transmission from primary afferents onto medullary dorsal horn neurons. In this study, we have addressed the cholinergic modulation of primary afferent glutamatergic transmission using a conventional whole cell patch clamp technique. Glutamatergic excitatory postsynaptic currents (EPSCs) were evoked from primary afferents by electrical stimulation of trigeminal tract and monosynaptic EPSCs were recorded from medullary dorsal horn neurons of rat horizontal brain stem slices. Muscarine and ACh reversibly and concentration-dependently decreased the amplitude of glutamatergic EPSCs and increased the paired-pulse ratio. In addition, muscarine reduced the frequency of miniature EPSCs without affecting the current amplitude, suggesting that muscarine acts presynaptically to decrease the probability of glutamate release onto medullary dorsal horn neurons. The muscarine-induced decrease of glutamatergic EPSCs was significantly occluded by methoctramine or AF-DX116, M2 receptor antagonists, but not pirenzepine, J104129 and MT-3, selective M1, M3 and M4 receptor antagonists. The muscarine-induced decrease of glutamatergic EPSCs was highly dependent on the extracellular Ca2+ concentration. Physostigmine and clinically available acetylcholinesterase inhibitors, such as rivastigmine and donepezil, significantly shifted the concentration-inhibition relationship of ACh for glutamatergic EPSCs. These results suggest that muscarine acts on presynaptic M2 receptors to inhibit glutamatergic transmission by reducing the Ca2+ influx into primary afferent terminals, and that M2 receptor agonists and acetylcholinesterase inhibitors could be, at least, potential targets to reduce nociceptive transmission from orofacial tissues. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/23954675/Cholinergic_modulation_of_primary_afferent_glutamatergic_transmission_in_rat_medullary_dorsal_horn_neurons_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(13)00347-X DB - PRIME DP - Unbound Medicine ER -