Ⅰ组代谢型谷氨酸受体激活调制脊髓运动神经元的下行激活

中国临床药理学与治疗学 ›› 2011, Vol. 16 ›› Issue (12): 1374-1378.

Ⅰ组代谢型谷氨酸受体激活调制脊髓运动神经元的下行激活

郑勇, 汪萌芽

皖南医学院细胞电生理研究室, 芜湖 241002, 安徽

收稿日期:2011-04-27 修回日期:2011-09-01 出版日期:2011-12-26 发布日期:2012-01-07
通讯作者: 汪萌芽,通信作者,男,博士,教授,硕士生导师,研究方向:神经细胞电生理学与药理学。Tel: 0553-3932276 E-mail: wangmy@wnmc.edu.cn
作者简介:郑勇,男,硕士研究生,研究方向:神经生理学。Tel: 15155333701 E-mail: xh.8917@163.com
基金资助:
安徽省自然科学基金(090413084)

Activation of group I metabotropic glutamate receptors modulates descending activation of spinal cord motoneurons

ZHENG Yong, WANG Meng-ya

Cell Electrophysiology Laboratory, Wannan Medical College, Wuhu 241002, Anhui, China

Received:2011-04-27 Revised:2011-09-01 Online:2011-12-26 Published:2012-01-07

摘要/Abstract

摘要： 目的: 探讨I组代谢型谷氨酸受体(mGluRs)激活对离体脊髓运动神经元(MN)下行激活的调制作用。方法: 应用新生大鼠(7~14 d)脊髓切片MN细胞内记录技术,记录脊髓同侧腹外侧索(iVLF)电刺激诱发的兴奋性突触后电位(EPSP,即iVLF-EPSP),观察I组mGluRs激动剂(S)-3,5-二羟基苯基甘氨酸(DHPG)对MN膜电学特性及iVLF-EPSP的影响。结果: 对脊髓切片灌流DHPG(5 μmol/L),能使MN膜去极化(n=7,P<0.01),缩短时间常数(n=7,P<0.05),并延长锋电位的半幅时程(n=5,P<0.05)。同时,给予DHPG(5~10 μmol/L)能可逆性、浓度依赖性抑制iVLF-EPSP的幅度(n=7,P<0.01)。结论: DHPG对I组mGluRs的激活对离体脊髓MN的下行激活有抑制性调制作用。

关键词: 运动神经元, 脊髓, 代谢型谷氨酸受体, 下行激活, (S)-3,5-二羟基苯基甘氨酸

Abstract: AIM: To evaluate the modulatory action of group I metabotropic glutamate receptors (mGluRs) on descending activation of spinal cord motoneurons (MNs) in vitro.METHODS: The intracellular recordings were made in MNs of spinal cord slices isolated from neonatal rats (7-14 days old), and excitatory postsynaptic potential (EPSP) was evoked by ipsilateral ventrolateral funiculus (iVLF) stimulation, i.e. iVLF-EPSP.By superfusion of (S)-3,5-dihydroxyphenylglycine hydrate (DHPG), an agonist of group I mGluRs, the modulatory action was observed on the MN membrane electrical properties, as well as on the iVLF-EPSP.RESULTS: Application of DHPG (5 μmol/L) significantly depolarized the motoneuron membrane (n=7, P<0.01), reduced time constant (n=7, P<0.05), and extended the half-width of the spike potential (n=5, P<0.05). The amplitude of iVLF-EPSPs in 7 tested MNs was reversibly and concentration-dependently suppressed by superfusion of DHPG (5-10 μmol/L,P<0.01).CONCLUSION: Activation of group I mGluRs by DHPG may inhibit the descending activation of spinal cord MNs in vitro.

Key words: Motoneuron, Spinal cord, Metabotropic glutamate receptor, Descending activation, (S)-3,5-dihydroxyphenylglycine hydrate(DHPG)

中图分类号:

R965.2

郑勇, 汪萌芽. Ⅰ组代谢型谷氨酸受体激活调制脊髓运动神经元的下行激活[J]. 中国临床药理学与治疗学, 2011, 16(12): 1374-1378.

ZHENG Yong, WANG Meng-ya. Activation of group I metabotropic glutamate receptors modulates descending activation of spinal cord motoneurons[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2011, 16(12): 1374-1378.

参考文献

[1] Pin JP, Duvoisin R.The metabotropic glutamate receptors:structure and functions[J]. Neuropharmacology, 1995, 34(1): 1-26.
[2] Nistri A, Ostroumov K, Sharifullina E, et al.Tuning and playing a motor rhythm: how metabotropic glutamate receptors orchestrate generation of motor patterns in the mammalian central nervous system [J].J Physiol, 2006, 572(2): 323-334.
[3] Toccola G, Marchetti C, Nistri A. Role of group Ⅱ and Ⅲ metabotropic glutamate receptors in rhythmic patterns of the neonatal rat spinal cord in vitro [J]. Exp Brain Res, 2004, 156(4): 495-504.
[4] Guo W, Wei F, Ren K, et al.GroupⅠmetabotropic glutamate receptor NMDA receptor coupling and signaling cascade mediate spinal dorsal horn NMDA receptor 2B tyrosine phosphorylation associated with inflammatory hyperalgesia[J]. J Neurosci, 2004, 24(41): 9161-9173.
[5] Chen SR, Pan HL. Distinct roles of group Ⅲ metabotropic glutamate receptors in control of nociception and dorsal horn neurons in normal and nerve-injured Rats[J].J Pharmacol Exp Ther, 2005, 312(1): 120-126.
[6] 李胜光, 张艳, 汪萌芽.代谢型谷氨酸受体对脊髓背根向运动神经元传入的调制作用[J]. 皖南医学院学报, 2007, 26(4): 241-244.
[7] Arvanian VL, Motin V, Mendell LM.Comparison of metabotropic glutamate receptorrespones at segmental and descending inputs to motoneurons in neonatal rat spinal cord[J]. J Pharmacol Exp Ther, 2005, 312(2): 669-677.
[8] Machetti C, Taccola G, Nistri A.Distinct subtypes of groupⅠmetabotropic glutamate receptors on rat spinal neurons mediate complex facilitatory and inhibitory effects [J].Eur J Neurosci, 2003, 18(7): 1873-1883.
[9] 汪萌芽. 新生大鼠脊髓切片运动神经元的电生理参数测定[J].中国应用生理学杂志, 1993, 9(2): 164-167.
[10] 汪萌芽. 新生大鼠脊髓薄片的运动神经元对腹外侧索刺激的反应[J]. 生理学报, 1994, 46(2): 148-153.
[11] 汪萌芽, 沈锷. 离体运动神经元对腹外侧索刺激的突触反应特征[J].生理学报, 1997, 49(6): 625-631.
[12] 吴丽丽, 严灿, 徐志伟. 代谢型谷氨酸受体与应激损伤[J]. 中国药理学通报, 2004, 20(2): 125-128.
[13] Vernon AC, Croucher MJ, Dexter DT. Additive neuroprotection by metabotropic glutamate receptor subtype-selective ligands in a rat Parkinson's model [J]. Neuroreport, 2008, 19(4): 475-478.
[14] Awad H, Hubert GW, Smith Y, et al. Activation of metabotropic glutamate receptor 5 has direct excitatory effects and potentiates NMDA receptor currents in neurons of the subthalamic nucleus [J]. J Neurosci, 2000, 20(21): 7871-7879.
[15] Marino MJ, Wittmann M, Bradley SR.Activation of group I metabotropic glutamate receptors produces a direct excitation and disinhibition of GABAergic projection neurons in the substantia nigra pars reticulate [J]. J Neurosci, 2001, 21(18): 7001-7012.
[16] Iwagaki N, Miles GB. Activation of group I metabotropic glutamate receptors modulates locomotor-related motoneuron output in mice[J].J Neurophysiol, 2011,105(5):2108-2120.
[17] Park YK, Galik J, Randic M, et al. Activation of presynaptic GroupⅠmetabotropic glutamate receptor enhances glutamate release in the rat spinal cord substantia gelatinosa [J]. Neurosci Lett, 2004, 361(1/2/3): 220-224.
[18] Heidinger V, Manzerra P, Wang XQ, et al. Metabotropic glutamate receptor 1-induced upregulation of NMDA receptor current: mediation through Pyk2/Src-family kinase pathway in cortical neurons [J]. J Neurosci, 2002, 22(13): 5452-5461.
[19] Nakanishi S, Nakajima Y, Masu M, et al. Glutamate receptors: brain function and signal transduction[J]. Brain Res Brain Res Rev, 1998, 26(2/3): 230-235.
[20] Mannaioni G, Marino MJ, Valenti O, et al. Metabotropic glutamate receptors 1 and 5 differentially regulate CA1 pyramidal cell function[J].J Neurosci,2001, 21(16): 5925-5934.