Lipophilic compounds restore function to neurodevelopmental-associated KCNQ3 mutations.

ABSTRACT: A major driver of neuronal hyperexcitability is dysfunction of K⁺ channels, including voltage-gated KCNQ2/3 channels. Their hyperpolarized midpoint of activation and slow activation and deactivation kinetics produce a current that regulates membrane potential and impedes repetitive firing. Inherited mutations in KCNQ2 and KCNQ3 are linked to a wide spectrum of neurodevelopmental disorders (NDDs), ranging from benign familial neonatal seizures to severe epileptic encephalopathies and autism spectrum disorders. However, the impact of these variants on the molecular mechanisms underlying KCNQ3 channel function remains poorly understood and existing treatments have significant side effects. Here, we use voltage clamp fluorometry, molecular dynamic simulations, and electrophysiology

SUBMITTER: Edmond MA 

PROVIDER: S-EPMC11413209 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature