김은준 (KAIST, 기초과학연구원) | 한빛사논문 > 한빛사

한빛사논문

조회441

KAIST, 기초과학연구원

CV File 475 kb

Nat. Commun., 15 June 2023 | https://doi.org/10.1038/s41467-023-39203-z Kv7/KCNQ potassium channels in cortical hyperexcitability and juvenile seizure-related death in Ank2-mutant mice

Hyoseon Oh ^1,2, Suho Lee ², Yusang Oh ^1,3, Seongbin Kim ¹, Young Seo Kim ⁴, Yeji Yang ^1,5, Woochul Choi ³, Ye-Eun Yoo ², Heejin Cho ², Seungjoon Lee ², Esther Yang ⁶, Wuhyun Koh ⁷, Woojin Won ⁷, Ryunhee Kim ², C. Justin Lee ⁷, Hyun Kim ⁶, Hyojin Kang ⁸, Jin Young Kim ⁵, Taeyun Ku ⁴, Se-Bum Paik ³ & Eunjoon Kim ^1,2,*

¹Department of Biological Sciences, Korea Advanced Institute for Science and Technology (KAIST), Daejeon 34141, Korea.
²Center for Synaptic Brain Dysfunctions, Institute for Basic Science (IBS), Daejeon 34141, Korea.
³Department of Bio and Brain Engineering, KAIST, Daejeon 34141, Korea.
⁴Graduate School of Medical Science and Engineering, KAIST, Daejeon 34141, Korea.
⁵Research Center for Bioconvergence Analysis, Korea Basic Science Institute, 162 Yeongudanjiro, Ochang, Cheongju, Chungbuk 28119, Korea.
⁶Department of Anatomy and Brain Korea 21 Graduate Program, Biomedical Science, College of Medicine, Korea University, Seoul 02841, Korea.
⁷Center for Cognition and Sociality, IBS, Daejeon 34126, Korea.
⁸Division of National Supercomputing, Korea Institute of Science and Technology Information, Daejeon 34141, Korea.

*Corresponding author: correspondence to Eunjoon Kim

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.

논문정보

형식Research article
게재일2023년 06월 (BRIC 등록일 2023-06-16)
연구진국내 연구진
분야 생명과학 > 생리학

댓글 작성 로그인

CV 열람하기

연락처 보기