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

Nature communications 2023 Jun 15

filter terms:

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. © 2023. The Author(s).

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 Lee, Hyun Kim, Hyojin Kang, Jin Young Kim, Taeyun Ku, Se-Bum Paik, Eunjoon Kim. Kv7/KCNQ potassium channels in cortical hyperexcitability and juvenile seizure-related death in Ank2-mutant mice. Nature communications. 2023 Jun 15;14(1):3547