INVOLVEMENT OF GABA AND GLYCINE IN RECURRENT INHIBITION OF SPINAL MOTONEURONS
INVOLVEMENT OF GABA AND GLYCINE IN RECURRENT INHIBITION OF SPINAL MOTONEURONS
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DOI：
10.1152/jn.1992.68.2.397
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发表时间：
1992-08-01
影响因子：
2.5
通讯作者：
FYFFE, REW
中科院分区：
文献类型：
--
作者：
SCHNEIDER, SP;FYFFE, REW
1.在新生大鼠（5- 12天）的离体腰髓中，从细胞内记录氯化物负载的运动神经元的反复抑制性突触后电位（IPSPs）。该体外制备物显示出完整的和功能性的复发抑制通路，其显示了先前在其他物种中描述的该通路的特征。尽管士的宁（1-5 μ M）抑制了由腹根刺激诱发的氯依赖性复发性突触电位48.2 +/- 2.7%（平均值+/- SE，n = 13），证实了复发性IPSP的一部分是由甘氨酸能机制介导的，但在每种情况下，都抑制了残余的士的宁抗性突触电位.低浓度（2-10 μ M）的γ-氨基丁酸（GABA）拮抗剂荷包牡丹碱以剂量依赖性方式抑制了27.0 +/- 4.3%（范围0- 49%，n = 19）的复发性突触电位。荷包牡丹碱的应用几乎消除了IPSP的士的宁耐药组分。士的宁和荷包牡丹碱合用后，部分运动神经元仍有少量的突触电位. GABA摄取的选择性拮抗剂，（+/-）-哌啶甲酸（1 mM）和guvacine（1 mM），增加了37.2 - 7.2%（范围12.6-84.2%）的12个16运动神经元的复发性突触电位的幅度。5.兴奋性氨基酸拮抗剂犬尿烯酸（1 mM）、6-氰基-7-硝基喹喔啉-2，3-二酮[CNQX（10 μ M）]和6，7-二硝基喹喔啉-2，3-二酮（10 μ M）在7个运动神经元中的5个中增强了复发性突触电位。然而，CNQX（10-15 μ M）在士的宁和荷包牡丹碱的存在下，几乎取消了突触电位后，应用抑制性氨基酸拮抗剂剩余。结论：前根刺激引起新生大鼠运动神经元兴奋性氨基酸介导的突触电位.由于运动神经元之间的电紧张性耦合的逆向突触电位不受膜电位、氯离子负荷或甘氨酸、GABA、兴奋性氨基酸和乙酰胆碱受体的拮抗剂的变化的影响。结果表明，一个主要部分的士的宁耐药组分的IPSP介导的GABA能机制。结论：甘氨酸能和GABA能机制在哺乳动物脊髓运动神经元的反复抑制中发挥作用。目前还不清楚这些抑制性氨基酸是由单个Renshaw细胞库还是由神经化学上不同的群体释放的。
1. Recurrent inhibitory postsynaptic potentials (IPSPs) were recorded intracellularly from chloride-loaded motoneurons in the isolated lumbar spinal cord of neonatal rats (day 5-day 12). This in vitro preparation exhibited an intact and functional recurrent inhibitory pathway that displayed characteristics previously described for this pathway in other species.2. Although strychnine (1-5-mu-M) depressed the chloride-dependent recurrent synaptic potentials evoked by ventral root stimulation by 48.2 +/- 2.7% (mean +/- SE, n = 13), confirming that part of the recurrent IPSP is mediated by a glycinergic mechanism, in every case a residual strychnine-resistant synaptic potential was observed.3. The gamma-aminobutyric acid (GABA) antagonist bicuculline, in low concentrations (2-10-mu-M), depressed the recurrent synaptic potentials in a dose-dependent manner by 27.0 +/- 4.3% (range 0-49%, n = 19). Application of bicuculline almost eliminated the strychnine-resistant component of the IPSP. However, in some motoneurons, a small synaptic potential remained after combined application of strychnine and bicuculline.4. The selective antagonists of GABA uptake, (+/-)-nipecotic acid (I mM) and guvacine (I mM), increased the amplitude of recurrent synaptic potentials in 12 of 16 motoneurons by 37.2 7.2% (range 12.6-84.2%).5. The excitatory amino acid antagonists kynurenic acid (1 mM), 6-cyano-7-nitroquinoxoline-2,3-dione [CNQX (10-mu-M)] and 6,7-dinitroquinoxaline-2,3-dione (10-mu-M) potentiated recurrent synaptic potentials in 5 of 7 motoneurons. However, CNQX (10-15-mu-M) in the presence of strychnine and bicuculline virtually abolished the synaptic potential remaining after application of the inhibitory amino acid antagonists. It is concluded that ventral root stimulation evokes a small excitatory amino acid-mediated synaptic potential in neonatal rat motoneurons.6. An antidromic synaptic potential due to electrotonic coupling between motoneurons was unaffected by changes in membrane potential, chloride loading, or antagonists of glycine, GABA, excitatory amino acid, and acetylcholine receptors.7. The results suggest that a major portion of the strychnine-resistant component of the IPSP is mediated by a GABAergic mechanism. It is concluded that both glycinergic and GABAergic mechanisms play a role in recurrent inhibition of motoneurons in the mammalian spinal cord. It is unknown whether these inhibitory amino acids are released by a single pool of Renshaw cells or by neurochemically distinct populations.