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首页> 外文期刊>Journal of Neurophysiology >Dual mechanisms diminishing tonic GABAA inhibition of dentate gyrus granule cells in Noda epileptic rats
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Dual mechanisms diminishing tonic GABAA inhibition of dentate gyrus granule cells in Noda epileptic rats

机译:核苷酸癫痫大鼠牙齿血清颗粒细胞滋补GABAA抑制的双重机制

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摘要

The Noda epileptic rat (NER), a Wistar colony mutant, spontaneously has tonicclonic convulsions with paroxysmal discharges. In the present study, we measured phasic and tonic γ-aminobutyric acid A (GABAA) current (Itonic) in NER hippocampal dentate gyrus granule cells and compared the results with those of normal parent strain Wistar rats (WIS). Itonic, revealed by a bicuculline-induced outward shift in holding current, was significantly smaller in NER than in WIS (P 0.01). The frequency of inhibitory postsynaptic currents (IPSCs) was also significantly lower in NER than in WIS (P 0.05), without significant differences in the IPSC amplitude or decay time between WIS and NER. Itonicattenuation in NER was further confirmed in the presence of GABA transporter blockers, NO-711 and nipecotic acid, with no difference in neuronal GABA transporter expression between WIS and NER. Itonicresponses to extrasynaptic GABAAreceptor agonists (THIP and DS-2) were significantly reduced in NER compared with WIS (P 0.05). Allopregnanolone caused less Itonicincrease in NER than in WIS, while it prolonged the IPSC decay time to a similar rate in the two groups. Expression of the GABAAreceptor δ-subunit was decreased in the dentate gyrus of NER relative to that of WIS. Taken together, our results showed that a combination of attenuated presynaptic GABA release and extrasynaptic GABAAreceptor expression reduced Itonicamplitude and its sensitivity to neurosteroids, which likely diminishes the gating function of dentate gyrus granule cells and renders NER more susceptible to seizure propagation.
机译:Noda癫痫大鼠(ner),Wistar菌落突变体,自发地具有阵发性排放的曲氏曲调痉挛。在本研究中,我们在Ner海马齿状颗粒细胞中测量相位和滋补γ-氨基丁酸A(GABAA)电流(轶事),并将结果与​​正常亲本菌株Wistar大鼠(WIS)进行比较。通过Biculline诱导的保持电流向外移位揭示的轶事,比WIS(P <0.01)显着更小。抑制后突触电流(IPSC)的频率也比WIS(P <0.05)中的不显着低,在WIS和NER之间的IPSC幅度或衰减时间内没有显着差异。在GABA转运蛋白阻滞剂,NO-711和NIPecotic acid存在下进一步证实了NER中的肌音陈,在WIS和NER之间的神经元GABA转运蛋白表达没有差异。与WIS(P <0.05)相比,NER中,对额外越突触的高肾上腺激动剂(Thip和DS-2)显着降低(P <0.05)。 allopregnanolone在ner中造成的次数不如wis,而它延长了IPSC衰减时间在两组中的类似速率。相对于WIS的牙齿的牙齿波动转酯中,GabaereceptorΔ-亚基的表达降低。我们的结果表明,减毒的突触前GABA释放和额外的Gabaere表达表达的组合降低了思想致血压和神经活体的敏感性,这可能降低了牙齿颗粒细胞的牙齿颗粒细胞的门控功能,并且呈现易于癫痫发作繁殖。

著录项

  • 来源
    《Journal of Neurophysiology》 |2013年第1期|共8页
  • 作者单位

    Department of Physiology School of Medicine and Brain Research Institute Chungnam National;

    Department of Physiology School of Medicine and Brain Research Institute Chungnam National;

    Department of Physiology School of Medicine and Brain Research Institute Chungnam National;

    Department of Physiology School of Medicine and Brain Research Institute Chungnam National;

    Department of Anamomy School of Medicine and Brain Research Institute Chungnam National;

    Department of Neurology School of Medicine and Brain Research Institute Chungnam National;

    Laboratory of Veterinary Pharmacology College of Veterinary Medicine Seoul National University;

    Laboratory of Veterinary Pharmacology College of Veterinary Medicine Seoul National University;

    Department of Physiology School of Medicine and Brain Research Institute Chungnam National;

    Department of Physiology School of Medicine and Brain Research Institute Chungnam National;

    Department of Physiology School of Medicine and Brain Research Institute Chungnam National;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 人体生理学;
  • 关键词

    Dentate gyrus granule cells; GABAA receptors; Noda epileptic rat;

    机译:牙齿gyrus颗粒细胞;gabaa受体;核心癫痫大鼠;

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