Gluconate suppresses seizure activity in developing brains by inhibiting CLC-3 chloride channels
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..
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2019 |
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| Erschienen: |
2019 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Molecular brain - 12(2019), 1 vom: 15. Mai |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wu, Zheng [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| Themen: |
Anticonvulsant |
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| Anmerkungen: |
© The Author(s). 2019 |
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| doi: |
10.1186/s13041-019-0465-0 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
SPR029596653 |
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| 520 | |a 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. | ||
| 650 | 4 | |a Neonatal seizure |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Epilepsy |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Gluconate |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Anticonvulsant |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a CLC-3 |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a Chloride channels |7 (dpeaa)DE-He213 | |
| 650 | 4 | |a GABA |7 (dpeaa)DE-He213 | |
| 700 | 1 | |a Huo, Qingwei |4 aut | |
| 700 | 1 | |a Ren, Liang |4 aut | |
| 700 | 1 | |a Dong, Fengping |4 aut | |
| 700 | 1 | |a Feng, Mengyang |4 aut | |
| 700 | 1 | |a Wang, Yue |4 aut | |
| 700 | 1 | |a Bai, Yuting |4 aut | |
| 700 | 1 | |a Lüscher, Bernhard |4 aut | |
| 700 | 1 | |a Li, Sheng-Tian |4 aut | |
| 700 | 1 | |a Wang, Guan-Lei |4 aut | |
| 700 | 1 | |a Long, Cheng |4 aut | |
| 700 | 1 | |a Wang, Yun |4 aut | |
| 700 | 1 | |a Wu, Gangyi |4 aut | |
| 700 | 1 | |a Chen, Gong |0 (orcid)0000-0002-1857-3670 |4 aut | |
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