Skip to main content
Journal cover image

Neuronal mechanism of a BK channelopathy in absence epilepsy and dyskinesia.

Publication ,  Journal Article
Dong, P; Zhang, Y; Hunanyan, AS; Mikati, MA; Cui, J; Yang, H
Published in: Proc Natl Acad Sci U S A
March 22, 2022

A growing number of gain-of-function (GOF) BK channelopathies have been identified in patients with epilepsy and movement disorders. Nevertheless, the underlying pathophysiology and corresponding therapeutics remain obscure. Here, we utilized a knock-in mouse model carrying human BK-D434G channelopathy to investigate the neuronal mechanism of BK GOF in the pathogenesis of epilepsy and dyskinesia. The BK-D434G mice manifest the clinical features of absence epilepsy and exhibit severe motor deficits and dyskinesia-like behaviors. The cortical pyramidal neurons and cerebellar Purkinje cells from the BK-D434G mice show hyperexcitability, which likely contributes to the pathogenesis of absence seizures and paroxysmal dyskinesia. A BK channel blocker, paxilline, potently suppresses BK-D434G–induced hyperexcitability and effectively mitigates absence seizures and locomotor deficits in mice. Our study thus uncovered a neuronal mechanism of BK GOF in absence epilepsy and dyskinesia. Our findings also suggest that BK inhibition is a promising therapeutic strategy for mitigating BK GOF-induced neurological disorders.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

March 22, 2022

Volume

119

Issue

12

Start / End Page

e2200140119

Location

United States

Related Subject Headings

  • Seizures
  • Neurons
  • Mice
  • Large-Conductance Calcium-Activated Potassium Channels
  • Humans
  • Epilepsy, Absence
  • Dyskinesias
  • Channelopathies
  • Animals
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Dong, P., Zhang, Y., Hunanyan, A. S., Mikati, M. A., Cui, J., & Yang, H. (2022). Neuronal mechanism of a BK channelopathy in absence epilepsy and dyskinesia. Proc Natl Acad Sci U S A, 119(12), e2200140119. https://doi.org/10.1073/pnas.2200140119
Dong, Ping, Yang Zhang, Arsen S. Hunanyan, Mohamad A. Mikati, Jianmin Cui, and Huanghe Yang. “Neuronal mechanism of a BK channelopathy in absence epilepsy and dyskinesia.Proc Natl Acad Sci U S A 119, no. 12 (March 22, 2022): e2200140119. https://doi.org/10.1073/pnas.2200140119.
Dong P, Zhang Y, Hunanyan AS, Mikati MA, Cui J, Yang H. Neuronal mechanism of a BK channelopathy in absence epilepsy and dyskinesia. Proc Natl Acad Sci U S A. 2022 Mar 22;119(12):e2200140119.
Dong, Ping, et al. “Neuronal mechanism of a BK channelopathy in absence epilepsy and dyskinesia.Proc Natl Acad Sci U S A, vol. 119, no. 12, Mar. 2022, p. e2200140119. Pubmed, doi:10.1073/pnas.2200140119.
Dong P, Zhang Y, Hunanyan AS, Mikati MA, Cui J, Yang H. Neuronal mechanism of a BK channelopathy in absence epilepsy and dyskinesia. Proc Natl Acad Sci U S A. 2022 Mar 22;119(12):e2200140119.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

March 22, 2022

Volume

119

Issue

12

Start / End Page

e2200140119

Location

United States

Related Subject Headings

  • Seizures
  • Neurons
  • Mice
  • Large-Conductance Calcium-Activated Potassium Channels
  • Humans
  • Epilepsy, Absence
  • Dyskinesias
  • Channelopathies
  • Animals