Presynaptic inhibition of glutamatergic synaptic transmission to rat motoneurons by serotonin.
Presynaptic inhibition of glutamatergic synaptic transmission to rat motoneurons by serotonin.
复制标题
血清素对大鼠运动神经元的谷氨酸突触传递的突触前抑制。
DOI：
10.1152/jn.1996.76.2.799
复制
发表时间：
1996
期刊：
影响因子：
--
通讯作者：
Berger,AJ
中科院分区：
文献类型：
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作者：
Singer,JH;Bellingham,MC;Berger,AJ
1.在脑干切片制备中，我们记录了舌下神经运动神经元（HM）的兴奋性突触后电流（EPSC），该电流是由细胞外刺激诱发的，位于舌下神经运动核同侧的网状结构（n.十二）。5-羟色胺（5-HT）以剂量依赖性方式抑制突触能传递，如诱发的EPSC（eEPSC）峰值振幅降低至对照组（5-HT 10 μ M）的46 +/- 2%（平均值+/- SE，n = 26）所示。这种效应不是电压依赖性的，因为eEPSC逆转电位没有改变（n = 5）。此外，5-HT将eEPSC的上升速率降低至对照组的41 +/- 2%（n = 14）。用D（-）-2-氨基-5-膦酰基戊酸（50 μ M）阻断N-甲基-D-天冬氨酸受体通道或用6，7-二硝基-喹喔啉（20 μ M）阻断α-氨基-3-羟基-5-甲基-4-异恶唑丙酸/红藻氨酸受体通道并不改变5-HT对eEPSC振幅的相对降低（分别为n = 7和3）。2.在有河豚毒素的情况下（1 μ M），浴用5-HT并不减少由L-谷氨酸（1 mM）压力喷射到HM上引起的突触后谷氨酸电流（n = 5），它使自发性微型EPSC（mEPSC）的中位间期增加到对照组（n = 4）的178 +/- 12%，这表明5-HT在突触前起作用以减少囊泡释放的可能性。mEPSC振幅在四个细胞中的三个中轻微降低（中值振幅=对照的92 +/-3%）。3.特异性5-HT 1B受体激动剂[3-（1，2，5，6-四氢吡啶-4-基）吡咯并[3，2-B]吡啶-5-酮]（1 μ M）模拟5-HT对eEPSC的作用（eEPSC振幅降低至对照的31 +/-5%;上升率降低至对照组的40 +/- 4%，分别为n = 10和5）和mEPSC（中位事件间期增加至对照的231 +/- 36%;中位mEPSC振幅=对照的102 +/- 3%，n = 5）。此外，5-HT介导的抑制作用未被1-（2-甲氧基苯基）-4-[4-（2-邻苯二甲酰亚氨基）丁基]哌嗪氢溴酸盐（1 μ M）（一种5-HT 1A拮抗剂）和3-[2-[4-（4-氟苯甲酰基）-1-哌啶基]乙基]-2，4（1H，3 H）-喹唑啉二酮酒石酸盐（1 μ M）（一种5-HT 2A/2C拮抗剂）联合应用阻断（n = 4）。这些数据表明，5-HT的作用主要是5-HT 1B受体介导的。4.我们的结论是，5-HT，通过突触前5-HT 1B受体，抑制突触传递的囊泡释放的可能性减少。
1. In a brain stem slice preparation, we recorded glutamatergic excitatory postsynaptic currents (EPSCs) in hypoglossal motoneurons (HMs) evoked by extracellular stimulation in the reticular formation just ipsilateral to the hypoglossal motor nucleus (n. XII). Serotonin (5-HT) inhibited glutamatergic synaptic transmission in a dose-dependent fashion as indicated by a reduction in the evoked EPSC (eEPSC) peak amplitude to 46 +/- 2% (mean +/- SE, n = 26) of control (5-HT 10 microM). This effect was not voltage dependent, as the eEPSC reversal potential was not altered (n = 5). Additionally, 5-HT decreased the rate of rise of the eEPSC to 41 +/- 2% of control (n = 14). Blockade of N-methyl-D-aspartate-receptor-channels by D(-)-2-amino-5-phosphonopentanoic acid (50 microM) or of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/kainate receptor-channels by 6,7-dinitro-quinoxaline (20 microM) did not alter the relative reduction of the eEPSC amplitude by 5-HT (n = 7 and 3, respectively). 2. In the presence of tetrodotoxin (1 microM), bath application of 5-HT did not reduce postsynaptic glutamate currents elicited by pressure ejection of L-glutamate (1 mM) onto HMs (n = 5), and it increased the median interevent interval of spontaneous miniature EPSCs (mEPSCs) to 178 +/- 12% of control (n = 4), suggesting that 5-HT acts presynaptically to reduce the probability of vesicle release. mEPSC amplitude was decreased slightly in three of four cells (median amplitude = 92 +/- 3% of control). 3. The specific 5-HT1B receptor agonist [3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one] (1 microM) mimicked 5-HT in its effect on eEPSCs (eEPSC amplitude reduced to 31 +/- 5% of control; rate of rise reduced to 40 +/- 4% of control, n = 10 and 5, respectively) and mEPSCs (median interevent interval increased to 231 +/- 36% of control; median mEPSC amplitude = 102 +/- 3% of control, n = 5). Additionally, 5-HT-mediated inhibition was not blocked by coapplication of 1-(2-methoxyphenyl)-4-[4-(2-phthalimido) butyl] piperazine hydrobromide (1 microM), a 5-HT1A antagonist, and 3-[2-[4-(4-flurobenzoyl)-1-piperdinyl]ethyl]-2,4(1H,3H)-quin azolinedione tartrate (1 microM), a 5-HT2A/2C antagonist (n = 4). These data indicate that the 5-HT effect is primarily 5-HT1B receptor mediated. 4. We conclude that 5-HT, acting through presynaptic 5-HT1B receptors, inhibits glutamatergic synaptic transmission by reducing the probability of vesicle release.