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Dravet Syndrome: A Sodium Channel Interneuronopathy.
Current Opinion in Physiology 2018 April
Dravet Syndrome is a devastating childhood epilepsy disorder with high incidence of premature death plus comorbidities of ataxia, circadian rhythm disorder, impaired sleep quality, autistic-like social-interaction deficits and severe cognitive impairment. It is primarily caused by heterozygous loss-of-function mutations in the SCN1A gene that encodes brain voltage-gated sodium channel type-1, termed NaV 1.1. Here I review experiments on mouse genetic models that implicate specific loss of sodium currents and action potential firing in GABAergic inhibitory interneurons as the fundamental cause of Dravet Syndrome. The resulting imbalance of excitatory to inhibitory neurotransmission in neural circuits causes both epilepsy and co-morbidities. Promising therapeutic approaches involving atypical sodium channel blockers, novel drug combinations, and cannabidiol give hope for improved outcomes for Dravet Syndrome patients.
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