List of publications for week of April 4, 2022
Neuronal mechanism of a BK channelopathy in absence epilepsy and dyskinesia
(2022) Proceedings of the National Academy of Sciences of the United States of America, 119 (12), pp. e2200140119.
Dong, P.a , Zhang, Y.a , Hunanyan, A.S.b , Mikati, M.A.b c , Cui, J.d , Yang, H.a c
a Department of Biochemistry, Duke University Medical Center, Durham
b Department of Pediatrics, Duke University Medical Center, Durham
c Department of Neurobiology, Duke University Medical Center, Durham
d Department of Biomedical Engineering, Washington University in Saint Louis, MO, Saint Louis 63130, Seychelles
Abstract
SignificanceBK channelopathy has been increasingly implicated in diverse neurological disorders, including epilepsy and movement, cognitive, and neurodevelopmental disorders. However, precision medicine to treat BK channelopathy is lacking. We characterized a mouse model carrying a gain-of-function BK channelopathy D434G from a large family of patients with absence epilepsy and paroxysmal dyskinesia. The BK-D434G mice manifest the clinical features of absence seizures and exhibit severe locomotor defects including involuntary dyskinesia-like behavior. Pharmacological inhibition of BK channels suppresses neuronal hyperactivity and mitigates absence seizure and the locomotor defects. The BK-D434G mice thus serve as a model to understand the pathogenic mechanisms of absence epilepsy and dyskinesia. Our study also suggests that BK inhibition is a promising strategy for treating BK gain-of-function channelopathy.
Author Keywords
absence seizure; BK channel; channelopathy; dyskinesia; epilepsy
Document Type: Article
Publication Stage: Final
Source: Scopus