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
PY - 2007/1
Y1 - 2007/1
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 M2/M4 antagonist, or AFDX-116, a selective M2 antagonist, completely blocked the inhibitory effect of oxotremorine-M on monosynaptic EPSCs. However, the specific M4 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 M2 mAChRs play a critical role in the control of glutamatergic input from primary afferents to dorsal horn neurons. The M3 and M2/M4 subtypes on a subpopulation of interneurons are important for regulation of glutamate release from interneurons in the spinal dorsal horn.
AB - 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 M2/M4 antagonist, or AFDX-116, a selective M2 antagonist, completely blocked the inhibitory effect of oxotremorine-M on monosynaptic EPSCs. However, the specific M4 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 M2 mAChRs play a critical role in the control of glutamatergic input from primary afferents to dorsal horn neurons. The M3 and M2/M4 subtypes on a subpopulation of interneurons are important for regulation of glutamate release from interneurons in the spinal dorsal horn.
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U2 - 10.1152/jn.00586.2006
DO - 10.1152/jn.00586.2006
M3 - Article
C2 - 17050831
AN - SCOPUS:33846464673
SN - 0022-3077
VL - 97
SP - 102
EP - 109
JO - Journal of Neurophysiology
JF - Journal of Neurophysiology
IS - 1
ER -