Persistent Na⁺ current couples spreading depolarization to seizures in <i>Scn8a</i> gain of function mice.

ABSTRACT: Spreading depolarization (SD) is a slowly propagating wave of massive cellular depolarization that transiently impairs the function of affected brain regions. While SD typically arises as an isolated hemispheric event, we previously reported that reducing M-type potassium current (I_KM) by ablation of Kcnq2 in forebrain excitatory neurons results in tightly coupled spontaneous bilateral seizure-SD complexes in the awake mouse cortex. Here we find that enhanced persistent Na⁺ current due to gain-of-function (GOF) mutations in Scn8a (N1768D/+, hereafter D/+) produces a similar compound cortical excitability phenotype. Chronic DC-band EEG recording detected spontaneous bilateral seizure-SD complexes accompanied by seizures with a profound tonic motor compone

SUBMITTER: Aiba I 

PROVIDER: S-EPMC11482884 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature