| First Author | Dong P | Year | 2022 |
| Journal | Proc Natl Acad Sci U S A | Volume | 119 |
| Issue | 12 | Pages | e2200140119 |
| PubMed ID | 35286197 | Mgi Jnum | J:337228 |
| Mgi Id | MGI:7257739 | Doi | 10.1073/pnas.2200140119 |
| Citation | Dong P, et al. (2022) Neuronal mechanism of a BK channelopathy in absence epilepsy and dyskinesia. Proc Natl Acad Sci U S A 119(12):e2200140119 |
| abstractText | 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. |
