Neuronal mechanism of a BK channelopathy in absence epilepsy and dyskinesia

Ping Dong, Yang Zhang, Arsen S. Hunanyan, Mohamad A. Mikati, Jianmin Cui, Huanghe Yang

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


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.

Original languageEnglish
Article numbere2200140119
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number12
StatePublished - Mar 22 2022


  • Absence seizure
  • BK channel
  • Channelopathy
  • Dyskinesia
  • Epilepsy


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