...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>The European Journal of Neuroscience >An impaired neocortical I is associated with enhanced excitability and absence epilepsy.
【24h】

An impaired neocortical I is associated with enhanced excitability and absence epilepsy.

机译：新皮质I受损与兴奋性增强和癫痫发作无关。

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Abstract Neuronal subthreshold excitability and firing behaviour are markedly influenced by the activation and deactivation of the somato-dendritic hyperpolarization-activated cation current (I(h)). Here, we evaluated possible contributions of I(h) to hyperexcitability in an animal model of absence seizures (WAG/Rij rats). We investigated pyramidal neurons of the somatosensory neocortex, the site of generation of spike-wave discharges. I(h)-mediated functions in neurons from WAG/Rij rats, Wistar rats (sharing the same genetic background with WAG/Rij, but less epilepsy-prone) and ACI rats (an inbred strain, virtually free of seizures) were compared. We complemented whole-cell recordings from layer 2-3 pyramidal neurons with immunohistochemistry, Western blot and RT-PCR analysis of the h-channel subunits HCN1-4. The fast component of I(h) activation in WAG/Rij neurons was significantly reduced (50% reduction in the h-current density) and four times slower than in neurons from nonepileptic Wistar or ACI rats. The results showing decreases in currents corresponded to a 34% reduction in HCN1 protein in the WAG/Rij compared to the Wistar neocortex, but HCN1 mRNA showed stable expression. The other three I(h) subunit mRNAs and proteins (HCN2-4) were not affected. The alterations in I(h) magnitude and kinetics of gating in WAG/Rij neurons may contribute to augmented excitatory postsynaptic potentials, the increase in their temporal summation and the facilitation of burst firing of these neurons because each of these effects could be mimicked by the selective I(h) antagonist ZD 7288. We suggest that the deficit in I(h)-mediated functions may contribute to the development and onset of spontaneously occurring hyperexcitability in a rat model of absence seizures.
机译：摘要神经元亚阈值的兴奋性和放电行为受到体树突状细胞超极化激活阳离子电流（I（h））的激活和去激活的显着影响。在这里，我们评估了失神发作的动物模型（WAG / Rij大鼠）中I（h）对超兴奋性的可能贡献。我们研究了体感新皮质的锥体神经元，即尖峰波放电的产生部位。比较了WAG / Rij大鼠，Wistar大鼠（与WAG / Rij具有相同的遗传背景，但癫痫倾向较少）和ACI大鼠（自交系，几乎没有癫痫发作）的神经元中I（h）介导的功能。我们用免疫组化，Western印迹和H通道亚基HCN1-4的RT-PCR分析对2-3层锥体神经元的全细胞记录进行了补充。 WAG / Rij神经元中I（h）激活的快速成分被显着降低（h电流密度降低了50％），并且比非癫痫性Wistar或ACI大鼠的神经元慢了四倍。结果显示，与Wistar新皮层相比，电流减少相应于WAG / Rij中HCN1蛋白减少34％，但HCN1 mRNA显示稳定表达。其他三个I（h）亚基mRNA和蛋白质（HCN2-4）不受影响。 WAG / Rij神经元的I（h）大小和门控动力学的变化可能有助于增加兴奋性突触后电位，它们的时间总和的增加以及这些神经元爆发性放电的促进，因为这些作用中的每一个都可以被模拟。选择性I（h）拮抗剂ZD7288。我们建议I（h）介导的功能缺陷可能会导致失神发作的大鼠模型中自发发生的过度兴奋性的发生和发作。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号