K_Na1.1 gain-of-function preferentially dampens excitability of murine parvalbumin-positive interneurons.

ABSTRACT: KCNT1 encodes the sodium-activated potassium channel K_Na1.1, expressed preferentially in the frontal cortex, hippocampus, cerebellum, and brainstem. Pathogenic missense variants in KCNT1 are associated with intractable epilepsy, namely epilepsy of infancy with migrating focal seizures (EIMFS), and sleep-related hypermotor epilepsy (SHE). In vitro studies of pathogenic KCNT1 variants support predominantly a gain-of-function molecular mechanism, but how these variants behave in a neuron or ultimately drive formation of an epileptogenic circuit is an important and timely question. Using CRISPR/Cas9 gene editing, we introduced a gain-of-function variant into the endogenous mouse Kcnt1 gene. Compared to wild-type (WT) littermates, heterozygous and homozygous knock-in mice displayed g

SUBMITTER: Gertler TS 

PROVIDER: S-EPMC9169414 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature