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

Zheng Wu, Qingwei Huo, Liang Ren, Fengping Dong, Mengyang Feng, Yue Wang, Yuting Bai, Bernhard Luscher, Sheng Tian Li, Guan Lei Wang, Cheng Long, Yun Wang, Gangyi Wu, Gong Chen

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Article number50
JournalMolecular Brain
Volume12
Issue number1
DOIs
StatePublished - May 15 2019

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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