The input-output relationship of neuronal networks depends heavily on the intrinsic properties of their neuronal elements.Profound changes in intrinsic properties have been observed in various physiological and pathol...The input-output relationship of neuronal networks depends heavily on the intrinsic properties of their neuronal elements.Profound changes in intrinsic properties have been observed in various physiological and pathological processes,such as learning,memory and epilepsy.However,the cellular and molecular mechanisms underlying acquired changes in intrinsic excitability are still not fully understood.Here,we demonstrate that ERG3 channels are critically involved in the regulation of intrinsic excitability in hippocampal CA1 pyramidal neurons and DG granule cells.Knock-down of ERG3 channels significantly increases neuronal intrinsic excitability,which is mainly caused by decreased fast afterhyperpolarization,delayed time to the generation of an action potential and enhanced summation of somatic excitatory post-synaptic potentials.Interestingly,the expression level of ERG3 protein is significantly reduced in human and mouse brain tissues with temporal lobe epilepsy.Moreover,ERG3 channel knock-down in hippocampus significantly enhanced seizure susceptibility,while mice treated with ERG3 channel activator NS1643 were less prone to epileptogenesis.Taken together,our results suggest ERG3 channels play an important role in determining the excitability of hippocampal neurons and dysregulation of these channels may be involved in the generation of epilepsy.ERG3 channels may thus be a novel therapeutic target for the prevention of epilepsy.展开更多
红色毛癣菌(Trichophyton rubrum,T.rubrum)是皮肤癣最主要病原;侧柏叶(Cacumen Platycladi)是侧柏[Platycladus orientali s(L.)Franco]的干燥嫩枝梢及叶,被《苗族医学》收录用于治疗皮肤癣。本研究旨在探讨侧柏叶抗T.rubrum的主要活...红色毛癣菌(Trichophyton rubrum,T.rubrum)是皮肤癣最主要病原;侧柏叶(Cacumen Platycladi)是侧柏[Platycladus orientali s(L.)Franco]的干燥嫩枝梢及叶,被《苗族医学》收录用于治疗皮肤癣。本研究旨在探讨侧柏叶抗T.rubrum的主要活性物质及其抗真菌机制,为抗皮肤癣新药研发提供帮助。本研究通过测定最小抑菌浓度和孢子萌发率分析了侧柏叶活性物质对T.rubrum的抑菌活性,使用电镜观察T.rubrum菌丝形态和孢子超微结构,并检测侧柏叶活性物质对T.rubrum细胞膜通透性、完整性和麦角甾醇含量的影响,从而阐述侧柏叶活性物质对T.rubrum抑菌机理,最后采用GC-MS和qRT-PCR方法找到其抗T.rubrum的作用靶点。结果显示,侧柏叶石油醚部位的α-蒎烯为主要抗菌活性成分,MIC为32μg·mL^(-1),极显著抑制孢子萌发(P<0.01);α-蒎烯可致细胞膜发生明显损伤和内容物流出、通透性极显著增加(P<0.01)以及24 h内细胞膜中麦角甾醇和24(28)脱氢麦角甾醇含量显著下降(P<0.05);引起脂质色谱图中ERG3活性抑制相关的“麦角甾烷-7,24-二烯-3β-醇”色谱峰出现;可极显著降低ERG3的相对表达量(P<0.01)。结果表明,α-蒎烯是侧柏叶中发挥抗T.rubrum活性最主要成分且以ERG3为其抗真菌靶点。展开更多
文摘The input-output relationship of neuronal networks depends heavily on the intrinsic properties of their neuronal elements.Profound changes in intrinsic properties have been observed in various physiological and pathological processes,such as learning,memory and epilepsy.However,the cellular and molecular mechanisms underlying acquired changes in intrinsic excitability are still not fully understood.Here,we demonstrate that ERG3 channels are critically involved in the regulation of intrinsic excitability in hippocampal CA1 pyramidal neurons and DG granule cells.Knock-down of ERG3 channels significantly increases neuronal intrinsic excitability,which is mainly caused by decreased fast afterhyperpolarization,delayed time to the generation of an action potential and enhanced summation of somatic excitatory post-synaptic potentials.Interestingly,the expression level of ERG3 protein is significantly reduced in human and mouse brain tissues with temporal lobe epilepsy.Moreover,ERG3 channel knock-down in hippocampus significantly enhanced seizure susceptibility,while mice treated with ERG3 channel activator NS1643 were less prone to epileptogenesis.Taken together,our results suggest ERG3 channels play an important role in determining the excitability of hippocampal neurons and dysregulation of these channels may be involved in the generation of epilepsy.ERG3 channels may thus be a novel therapeutic target for the prevention of epilepsy.
