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Kv7/KCNQ potassium channels in cortical hyperexcitability and juvenile seizure-related death in Ank2-mutant mice

Author

Listed:
  • Hyoseon Oh

    (Korea Advanced Institute for Science and Technology (KAIST)
    Institute for Basic Science (IBS))

  • Suho Lee

    (Institute for Basic Science (IBS))

  • Yusang Oh

    (Korea Advanced Institute for Science and Technology (KAIST)
    Department of Bio and Brain Engineering)

  • Seongbin Kim

    (Korea Advanced Institute for Science and Technology (KAIST))

  • Young Seo Kim

    (Graduate School of Medical Science and Engineering)

  • Yeji Yang

    (Korea Advanced Institute for Science and Technology (KAIST)
    Korea Basic Science Institute)

  • Woochul Choi

    (Department of Bio and Brain Engineering)

  • Ye-Eun Yoo

    (Institute for Basic Science (IBS))

  • Heejin Cho

    (Institute for Basic Science (IBS))

  • Seungjoon Lee

    (Institute for Basic Science (IBS))

  • Esther Yang

    (Korea University)

  • Wuhyun Koh

    (IBS)

  • Woojin Won

    (IBS)

  • Ryunhee Kim

    (Institute for Basic Science (IBS))

  • C. Justin Lee

    (IBS)

  • Hyun Kim

    (Korea University)

  • Hyojin Kang

    (Korea Institute of Science and Technology Information)

  • Jin Young Kim

    (Korea Basic Science Institute)

  • Taeyun Ku

    (Graduate School of Medical Science and Engineering)

  • Se-Bum Paik

    (Department of Bio and Brain Engineering)

  • Eunjoon Kim

    (Korea Advanced Institute for Science and Technology (KAIST)
    Institute for Basic Science (IBS))

Abstract

Autism spectrum disorders (ASD) represent neurodevelopmental disorders characterized by social deficits, repetitive behaviors, and various comorbidities, including epilepsy. ANK2, which encodes a neuronal scaffolding protein, is frequently mutated in ASD, but its in vivo functions and disease-related mechanisms are largely unknown. Here, we report that mice with Ank2 knockout restricted to cortical and hippocampal excitatory neurons (Ank2-cKO mice) show ASD-related behavioral abnormalities and juvenile seizure-related death. Ank2-cKO cortical neurons show abnormally increased excitability and firing rate. These changes accompanied decreases in the total level and function of the Kv7.2/KCNQ2 and Kv7.3/KCNQ3 potassium channels and the density of these channels in the enlengthened axon initial segment. Importantly, the Kv7 agonist, retigabine, rescued neuronal excitability, juvenile seizure-related death, and hyperactivity in Ank2-cKO mice. These results suggest that Ank2 regulates neuronal excitability by regulating the length of and Kv7 density in the AIS and that Kv7 channelopathy is involved in Ank2-related brain dysfunctions.

Suggested Citation

  • Hyoseon Oh & Suho Lee & Yusang Oh & Seongbin Kim & Young Seo Kim & Yeji Yang & Woochul Choi & Ye-Eun Yoo & Heejin Cho & Seungjoon Lee & Esther Yang & Wuhyun Koh & Woojin Won & Ryunhee Kim & C. Justin , 2023. "Kv7/KCNQ potassium channels in cortical hyperexcitability and juvenile seizure-related death in Ank2-mutant mice," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39203-z
    DOI: 10.1038/s41467-023-39203-z
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    References listed on IDEAS

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