Kv7/KCNQ potassium channels in cortical hyperexcitability and juvenile seizure-related death in Ank2-mutant miceopen access
- Authors
- Oh, Hyoseon; Lee, Suho; Oh, Yusang; Kim, Seongbin; Kim, Young Seo; Yang, Yeji; Choi, Woochul; Yoo, Ye-Eun; Cho, Heejin; Lee, Seungjoon; Yang, Esther; Koh, Wuhyun; Won, Woojin; Kim, Ryunhee; Lee, C. Justin; Kim, Hyun; Kang, Hyojin; Kim, Jin Young; Ku, Taeyun; Paik, Se-Bum; Kim, Eunjoon
- Issue Date
- Jun-2023
- Publisher
- Nature Publishing Group
- Citation
- Nature Communications, v.14, no.1
- Indexed
- SCIE
SCOPUS
- Journal Title
- Nature Communications
- Volume
- 14
- Number
- 1
- URI
- https://scholarworks.korea.ac.kr/kumedicine/handle/2021.sw.kumedicine/63975
- DOI
- 10.1038/s41467-023-39203-z
- ISSN
- 2041-1723
2041-1723
- 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.
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- Appears in
Collections - 1. Basic Science > Department of Anatomy > 1. Journal Articles
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