毒蕈碱乙酰胆碱M2/M4受体亚型在调节脊髓背角神经元谷氨酸能递质释放中的作用

目的研究毒蕈碱胆碱能受体（mAChRs）亚型对脊髓背角感觉神经元谷氨酸能突触传递的调节机制。方法在急性切取
的腰段脊髓切片上，利用全细胞膜片钳法记录mAChRs非特异性激动剂氢化震颤素M（Oxo-M）对脊髓背角浅层神经元谷氨酸
能兴奋性突触后电流（eEPSCs）的影响，给予M2/M4受体特异性拮抗剂喜巴辛，观察mAChRs在脊髓背角浅层神经元谷氨酸能
递质释放调节过程中的作用。结果不同浓度Oxo-M使脊髓背角神经元单突触和多突触eEPSCs的幅度显著降低，其抑制强度
呈浓度依赖性，喜巴辛可以拮抗Oxo-M对刺激诱发eEPSCs幅度的抑制作用，在记录的25个细胞中，92.3%的单突触细胞和75%
的多突触细胞表现为Oxo-M抑制作用被完全拮抗，另有16%的细胞表现为部分拮抗作用。结论mAChRs激活后通过位于脊髓
背角传入神经末梢突触前膜的M2或M4受体亚型抑制兴奋性谷氨酸递质的释放，这种突触前对谷氨酸释放的调节可能是胆碱
能系统和mAChRs在脊髓水平对伤害性刺激调控的作用机制。

Role of muscarinic cholinergic receptor subtypes in regulating glutamatergic synaptic transmission in rat spinal dorsal horn

Objective To investigate the role of muscarinic cholinergic receptor (mAChR) subtypes in the regulation of
glutamatergic input to the spinal dorsal horn neurons and the possible mechanism. Methods Whole-cell voltage-clamp
recordings on acute spinal slice was utilized to investigate the effect of activation of mAChRs and blockade of M2/M4 subtypes
on glutamatergic synaptic transmission in rat spinal dorsal horn neurons. Results The nonselective mAChRs agonist
oxotremorine-M concentration-dependently decreased the amplitude of monosynaptic and polysynaptic evoked
glutamate-mediated excitatory postsynaptic currents (eEPSCs) in most of the neurons. The M2/M4 antagonist himbacine
completely blocked the inhibitory effect of oxotremorine-M in 92.3% of monosynaptic and 75% of polysynaptic neurons in the
spinal cord slices. In the remaining 16% neurons, himbacine partially blocked the inhibitory effect of oxotremorine-M.
Conclusions Activation of mAChRs in the spinal cord attenuates synaptic glutamate release to the dorsal horn neurons mainly
through M2 and M4 receptor subtypes, indicating that a presynaptic inhibition in the spinal cord may be involved in the
regulation of nociception by the cholinergic system and mAChRs.