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
复制标题
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
中科院分区:
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
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.
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影响因子:
5.6
作者:
Puskarjov M;Kahle KT;Ruusuvuori E;Kaila K
通讯作者:
Kaila K
影响因子:
3.7
作者:
Cleary RT;Sun H;Huynh T;Manning SM;Li Y;Rotenberg A;Talos DM;Kahle KT;Jackson M;Rakhade SN;Berry G;Jensen FE
通讯作者:
Jensen FE
影响因子:
9.3
作者:
Albertsson AM;Bi D;Duan L;Zhang X;Leavenworth JW;Qiao L;Zhu C;Cardell S;Cantor H;Hagberg H;Mallard C;Wang X
通讯作者:
Wang X
DOI:
10.1016/j.seizure.2011.04.013
发表时间:
2011-11
期刊:
Seizure
影响因子:
--
作者:
M. Belluzzo;Fabrizio Monti;Gilberto Pizzolato
通讯作者:
M. Belluzzo;Fabrizio Monti;Gilberto Pizzolato
影响因子:
48
作者:
Pressler, Ronit M.;Boylan, Geraldine B.;Zohar, Sarah
通讯作者:
Zohar, Sarah