Selective Na_V1.1 activation rescues Dravet syndrome mice from seizures and premature death.

ABSTRACT: Dravet syndrome is a catastrophic, pharmacoresistant epileptic encephalopathy. Disease onset occurs in the first year of life, followed by developmental delay with cognitive and behavioral dysfunction and substantially elevated risk of premature death. The majority of affected individuals harbor a loss-of-function mutation in one allele of SCN1A, which encodes the voltage-gated sodium channel Na_V1.1. Brain Na_V1.1 is primarily localized to fast-spiking inhibitory interneurons; thus the mechanism of epileptogenesis in Dravet syndrome is hypothesized to be reduced inhibitory neurotransmission leading to brain hyperexcitability. We show that selective activation of Na_V1.1 by venom peptide Hm1a restores the function of inhibitory interneurons from Dravet

SUBMITTER: Richards KL 

PROVIDER: S-EPMC6112713 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature