首页> 美国卫生研究院文献>The Journal of Physiology >Taurine activates excitatory non-synaptic glycine receptors on dopamine neurones in ventral tegmental area of young rats
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Taurine activates excitatory non-synaptic glycine receptors on dopamine neurones in ventral tegmental area of young rats

机译:牛磺酸激活幼鼠腹侧被盖区多巴胺神经元上的兴奋性非突触甘氨酸受体

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摘要

The physiological and pharmacological properties of taurine-induced responses were investigated in dopaminergic (DA) neurones from the ventral tegmental area (VTA) of young rats aged 1–13 postnatal days, either in acute brain slices or acutely dissociated neurones. When whole-cell responses were recorded from current-clamped neurones using the gramicidin-perforated technique, the application of taurine (0.01–30 mm) accelerated firings and induced membrane depolarization. In voltage-clamped neurones, taurine induced a current which was antagonized by strychnine and by picrotoxin, but not by bicuculline. In addition, taurine-induced current showed complete cross-desensitization with glycine-activated currents but not with γ-aminobutyric acid (GABA)-activated currents. Thus, taurine is a full agonist of the glycine receptors (GlyRs) in the VTA. Further studies found that taurine acted mainly on non-synaptic GlyRs. The application of 20 μm bicuculline abolished the spontaneous inhibitory post-synaptic currents (IPSCs) in 40/45 neurones, and 93% of the evoked IPSCs. The addition of 1 μm strychnine completely eliminated the remaining IPSCs. These results suggest that GABAergic IPSCs predominate, and that functional glycinergic synapses are present in a subset of the VTA neurones. The application of 1 μm strychnine alone induced an outward current, suggesting that these neurones were exposed to tonically released taurine/glycine. In conclusion, by activating non-synaptic GlyRs, taurine may act as an excitatory extra-synaptic neurotransmitter in the VTA during early development.
机译:在出生后1到13天的幼鼠的腹侧被盖区(VTA)的多巴胺能(DA)神经元中,在急性脑切片或急性分离的神经元中研究了牛磺酸诱导的反应的生理和药理特性。当使用青霉菌素穿孔技术从电流钳制的神经元记录全细胞反应时,牛磺酸(0.01– 30 mm)的应用会加速放电并诱导膜去极化。在电压钳制的神经元中,牛磺酸诱导产生的电流被士的宁和苦瓜毒素所拮抗,而不是被双小分子所拮抗。此外,牛磺酸诱导的电流显示出与甘氨酸激活的电流完全交叉脱敏,但没有被γ-氨基丁酸(GABA)激活的电流交叉脱敏。因此,牛磺酸是VTA中甘氨酸受体(GlyRs)的完全激动剂。进一步的研究发现,牛磺酸主要作用于非突触GlyRs。应用20μm双小分子消除了40/45神经元和93%诱发的IPSC中的自发抑制突触后电流(IPSC)。添加1μm的士丁宁可完全消除剩余的IPSC。这些结果表明,GABA能IPSCs占主导地位,而功能性甘氨酸突触存在于VTA神经元的子集中。单独施加1μm的士的宁会引起外向电流,表明这些神经元暴露于经调释的牛磺酸/甘氨酸。总之,通过激活非突触的GlyRs,牛磺酸在早期发育过程中可能充当VTA中兴奋性的突触外神经递质。

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