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

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 Lee, Hyun Kim, Hyojin Kang, Jin Young Kim, Taeyun Ku, Se Bum PaikEunjoon Kim

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


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.

Original languageEnglish
Article number3547
JournalNature communications
Issue number1
Publication statusPublished - 2023 Dec

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation (NRF) grant (2020M3E5D9080794 to H.Kim; 2022R1A2C3008991 to S.P.; 2021R1A2C2005294 to T.K.; 2022M3H9A2096186 to J.Y.K.), the Korea Institute of Science and Technology Information (K-21-L02-C10 to H.Kang), and the Institute for Basic Science, Korea (IBS-R002-D1 to E.K. and IBS-R001-D2 to C.J.L.).

Publisher Copyright:
© 2023, The Author(s).

ASJC Scopus subject areas

  • General Chemistry
  • General Biochemistry,Genetics and Molecular Biology
  • General Physics and Astronomy


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