Slack K⁺ channels limit kainic acid-induced seizure severity in mice by modulating neuronal excitability and firing.

ABSTRACT: Mutations of the Na⁺-activated K⁺ channel Slack (KCNT1) are associated with terrible epilepsy syndromes that already begin in infancy. Here we report increased severity of acute kainic acid-induced seizures in adult and juvenile Slack knockout mice (Slack^-/-) in vivo. Fittingly, we find exacerbation of cell death following kainic acid exposure in organotypic hippocampal slices as well as dissociated hippocampal cultures from Slack^-/- in vitro. Furthermore, in cultured Slack^-/- neurons, kainic acid-triggered Ca²⁺ influx and K⁺ efflux as well as depolarization-induced tetrodotoxin-sensitive inward currents are higher compared to the respective controls. This apparent changes in ion homeostasis could possibly explain

SUBMITTER: Skrabak D 

PROVIDER: S-EPMC10567740 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature