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Functional glycine receptor maturation in the absence of glycinergic input in dopaminergic neurones of the rat substantia nigra

机译:在大鼠黑质多巴胺能神经元中不存在甘氨酸输入的情况下功能性甘氨酸受体成熟

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摘要

The postnatal maturation pattern of glycine receptor channels (GlyRs) expressed by dopaminergic (DA) neurones of the rat substantia nigra pars compacta (SNc) was investigated using single-channel and whole-cell patch-clamp recordings in brain slices from rats aged 7–21 postnatal days (P). In neonatal rats (P7-P10), GlyRs exhibited a main conductance state of 100–110 pS with a mean open time of 16 ms. In juvenile rats (P19-P22), both the GlyR main conductance state (46-55 pS) and the mean open time (6.8 ms) were decreased. In neonatal rats, application of 30 μm picrotoxin, which is known to block homomeric GlyRs, strongly reduced glycine-evoked responses, while it was much less effective in juvenile rats. These results suggest that these GlyRs correspond functionally to α2 homomeric GlyRs in neonatal rats and α1/β heteromeric GlyRs in juvenile rats. A drastic but transient decrease in the glycine responsiveness of DA neurones occurred around P17 concomitant to the functional switch from the homomeric state to the heteromeric state. This age corresponds to a maturation phase for DA neurones. The application of 1 μm gabazine blocked spontaneous or evoked inhibitory synaptic current, while the addition of 1 μm strychnine had no effect, suggesting a lack of functional glycinergic synapses on DA neurones. Although it has been proposed that taurine is co-released with GABA at GABAergic synapses on DA neurones, in the present study the stimulation of GABAergic fibres failed to activate GlyRs. Blockade of taurine transporters and applications of high K+ and hyposmotic solutions were also unable to induce any strychnine-sensitive current. We conclude that functional maturation of GlyRs can occur in the absence of any detectable GlyR activation in DA neurones of the SNc.
机译:使用单通道和全细胞膜片钳记录,研究了7–岁大鼠的大脑切片中由黑质致密部(SNc)的多巴胺能(DA)神经元表达的甘氨酸受体通道(GlyRs)的出生后成熟模式。产后21天(P)。在新生大鼠(P7-P10)中,GlyRs的主要电导状态为100–110 pS,平均打开时间为16 ms。在幼年大鼠(P19-P22)中,GlyR主要电导状态(46-55 pS)和平均打开时间(6.8 ms)均降低。在新生大鼠中,使用已知可阻断同型GlyRs的30μm微小毒素,可大大降低甘氨酸诱发的反应,而在幼年大鼠中效果不佳。这些结果表明,这些GlyR在功能上对应于新生大鼠中的α2同聚GlyR和幼年大鼠中的α1/β异聚GlyR。 DA神经元的甘氨酸反应性急剧但短暂的降低发生在P17周围,伴随着功能从同质状态向异质状态的转换。该年龄对应于DA神经元的成熟阶段。施用1μm的gabazine会阻断自发或诱发的抑制性突触电流,而添加1μm的士的宁没有作用,表明缺乏对DA神经元的功能性甘油能突触。尽管已经提出牛磺酸在DA神经元的GABA能突触中与GABA共同释放,但在本研究中,刺激GABA能纤维未能激活GlyRs。牛磺酸转运蛋白的封锁以及高K + 和低渗溶液的应用也无法诱导任何对士的宁敏感的电流。我们得出结论,在SNc的DA神经元中没有任何可检测到的GlyR激活的情况下,GlyRs的功能成熟。

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