Zhang Hong-Mei, Chen Shao-Rui, Pan Hui-Lin
Department of Anesthesiology and Pain Medicine, The University of Texas M.D. Anderson Cancer Center, 1400 Holcombe Blvd., Unit 409, Houston, TX 77030, USA.
J Neurophysiol. 2007 Jan;97(1):102-9. doi: 10.1152/jn.00586.2006. Epub 2006 Oct 18.
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.
脊髓毒蕈碱型乙酰胆碱受体（mAChRs）的激活可产生镇痛作用，并通过增强GABA能/甘氨酸能张力和抑制谷氨酸能输入来抑制背角神经元。为了研究参与mAChR激动剂对谷氨酸释放抑制作用的mAChR亚型，在大鼠脊髓切片中使用全细胞记录法记录了II层神经元中诱发的兴奋性突触后电流（eEPSCs）。非选择性mAChR激动剂氧化震颤素-M浓度依赖性地抑制了由背根刺激诱发的单突触和多突触EPSCs。有趣的是，氧化震颤素-M对多突触EPSCs的抑制作用（64.7%）大于对单突触EPSCs的抑制作用（27.9%）。在用鞘内百日咳毒素预处理的大鼠中，氧化震颤素-M未能降低单突触EPSCs，但仍部分抑制了一些神经元中的多突触EPSCs。这种残留效应被相对选择性的M(3)拮抗剂4-DAMP阻断。M(2)/M(4)拮抗剂樟柳碱或选择性M(2)拮抗剂AFDX-116完全阻断了氧化震颤素-M对单突触EPSCs的抑制作用。然而，特异性M(4)拮抗剂MT-3并未改变氧化震颤素-M对单突触EPSCs的作用。樟柳碱在一些细胞中也部分减弱了氧化震颤素-M对多突触EPSCs的作用，而4-DAMP消除了这种作用。此外，氧化震颤素-M在22个神经元中的7个（31.8%）中显著降低了自发性EPSCs，这一作用被4-DAMP阻断。这项研究提供了新的信息，即M(2) mAChRs在控制从初级传入神经到背角神经元的谷氨酸能输入中起关键作用。中间神经元亚群上的M(3)和M(2)/M(4)亚型对于调节脊髓背角中间神经元的谷氨酸释放很重要。
