Gluconate suppresses seizure activity in developing brains by inhibiting CLC-3 chloride channels

Gluconate suppresses seizure activity in developing brains by inhibiting CLC-3 chloride channels
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葡萄糖酸盐通过抑制 CLC-3 氯通道来抑制发育中大脑的癫痫发作活动

DOI:
10.1186/s13041-019-0465-0
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发表时间:
2019-05
期刊:
影响因子:
3.6
通讯作者:
Chen Gong
Chen Gong
中科院分区:
医学3区
文献类型:
--
作者:
Wu Zheng;Huo Qingwei;Ren Liang;Dong Fengping;Feng Mengyang;Wang Yue;Bai Yuting;Luscher Bernhard;Li Sheng-Tian;Wang Guan-Lei;Long Cheng;Wang Yun;Wu Gangyi;Chen Gong

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Neonatal seizures are different from adult seizures, and many antiepileptic drugs that are effective in adults often fail to treat neonates. Here, we report that gluconate inhibits neonatal seizure by inhibiting CLC-3 chloride channels. We detect a voltage-dependent outward rectifying Cl−current mediated by CLC-3 Cl−channels in early developing brains but not adult mouse brains. Blocking CLC-3 Cl−channels by gluconate inhibits seizure activity both in neonatal brain slices and in neonatal animals with in vivo EEG recordings. Consistently, neonatal neurons of CLC-3 knockout mice lack the outward rectifying Cl−current and show reduced epileptiform activity upon stimulation. Mechanistically, we demonstrate that activation of CLC-3 Cl−channels alters intracellular Cl−homeostasis and enhances GABA excitatory activity. Our studies suggest that gluconate can suppress neonatal seizure activities through inhibiting CLC-3 Cl−channels in developing brains.
DOI: 10.1111/epi.12620
发表时间: 2014-06
期刊: Epilepsia
影响因子: 5.6
作者:
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DOI: 10.1016/j.seizure.2011.04.013
发表时间: 2011-11
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通讯作者: Zohar, Sarah