Neuronal mechanism of a BK channelopathy in absence epilepsy and dyskinesia

A growing number of gain-of-function (GOF) BK channelopathies have been identified 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.

Automated summary

An increasing number of gain-of-function BK channelopathies have been found to be associated with motor deficits and dyskinesia-like behaviors. Our study reveals the neuronal mechanism of BK gain-of-function in absence epilepsy and dyskinesia, and suggests that BK inhibition is a promising therapeutic strategy for BK gain-of-function-induced neurological disorders.