Proceedings of the National Academy of Sciences · 2017 · 100 citations · 51 references
Life SciencesNeurobiologyNeuroscienceCellular NeuroscienceElectrophysiologyEpilepsyChannelopathiesGenetic EpilepsiesIon Channel DisordersNeural ExcitabilityNeuronal ExcitabilitySodium Channel BiophysicsChannelopathy GenesChannelopathy MutationsCurrent DensityEpileptic ChannelopathiesPersistent Sodium CurrentSodium Channel Gene DisordersSodium Channel GenesVoltage-gated Sodium Channels
Significance Patients with early infantile epileptic encephalopathy experience severe seizures and cognitive impairment and are at increased risk for sudden unexpected death in epilepsy (SUDEP). Here, we investigated the neuronal phenotype of a mouse model of early infantile epileptic encephalopathy (EIEE) 13 caused by a mutation in the sodium channel gene SCN8A . We found that excitatory and inhibitory neurons from mutant mice had increased persistent sodium current density. Measurement of action potential firing in brain slices from mutant mice revealed hyperexcitability with spontaneous firing in a subset of neurons. These changes in neurons are predicted to contribute to the observed seizure phenotype in whole animals. Our results provide insights into the disease mechanism and future treatment of patients with EIEE13.
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De novo mutations in epileptic encephalopathies
Krishna R. Veeramah, Janelle E. O’Brien, Miriam H. Meisler et al. · The American Journal of Human Genetics · 2012 · 439 citations · Full text