Cao C Q, Tse H W, Jane D E, Evans R H, Headley P M
Department of Pharmacology, School of Medical Sciences, Bristol, U.K.
Neuropharmacology. 1997 Mar;36(3):313-8. doi: 10.1016/s0028-3908(96)00180-3.
The patch-clamp technique has been used to record synaptic responses, elicited by electrical stimulation of dorsal roots, in 28 single motoneurones of in vitro spinal cord preparations from neonate (P5 to P8) rats. The effects of (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG) (200 microM), a potent antagonist at L-2-amino-4-phosphonobutanoate (AP4)-sensitive receptors, and (RS)-alpha-methyl-4-carboxyphenylglycine (MCPG) (500 microM), which is a less selective antagonist of mGluRs, were tested on EPSCs alone and as antagonists of AP4-induced depression of EPSCs. The EC50 for depression of EPSCs by AP4 (1.16 +/- 0.12 microM, n = 8) was increased to 18.9 +/- 0.7 microM (n = 6) by MPPG. MCPG (500 microM) had no significant effect on the depressant potency of AP4. Under control conditions, EPSCs had mean peak amplitudes of 983 pA +/- 64 SEM and mean charge transferred of 306 +/- 37 pC (n = 28). These values were increased significantly (p < 0.05) to 1168 +/- 68 pA and 363 +/- 39 pC by MPPG (n = 6), and 1150 +/- 54 pA and 358 +/- 33 pC (n = 6) by MCPG. There was no significant difference between the enhancement of the initial peak of the EPSCs (mean latency from stimulus artifact 5.9 +/- 0.3 ms) and later components, suggesting mGluRs to be present on primary afferent terminals presynaptic to motoneurones as well as in pathways via interneurones. These results are consistent with the presence of at least two types of presynaptic mGluR that modulate release of glutamate in segmental pathways convergent onto motoneurones. These receptors appear to be activated by interstitial glutamate tonically present in the present preparations.
膜片钳技术已用于记录新生（P5至P8）大鼠体外脊髓制备物中28个单运动神经元由背根电刺激引发的突触反应。测试了（RS）-α-甲基-4-膦酰基苯甘氨酸（MPPG）（200 microM）（一种对L-2-氨基-4-膦酰基丁酸（AP4）敏感受体的强效拮抗剂）和（RS）-α-甲基-4-羧基苯甘氨酸（MCPG）（500 microM）（一种对代谢型谷氨酸受体（mGluRs）选择性较低的拮抗剂）对兴奋性突触后电流（EPSCs）的单独作用以及作为AP4诱导的EPSCs抑制的拮抗剂的作用。AP4使EPSCs抑制的半数有效浓度（EC50）（1.16±0.12 microM，n = 8）被MPPG提高到18.9±0.7 microM（n = 6）。MCPG（500 microM）对AP4的抑制效力无显著影响。在对照条件下，EPSCs的平均峰值幅度为983 pA±64 SEM，平均电荷转移量为306±37 pC（n = 28）。这些值被MPPG（n = 6）显著提高（p < 0.05）至1168±68 pA和363±39 pC，被MCPG（n = 6）提高至1150±54 pA和358±33 pC。EPSCs初始峰值（刺激伪迹后的平均潜伏期为5.9±0.3 ms）与后期成分的增强之间无显著差异，这表明mGluRs存在于运动神经元突触前的初级传入终末以及通过中间神经元的通路中。这些结果与至少两种类型的突触前mGluR的存在一致，它们调节汇聚到运动神经元的节段性通路中谷氨酸的释放。这些受体似乎被本制备物中持续存在的细胞间谷氨酸激活。
