Translational Research in Epilepsy GeneticsSodium Channels in Man to Interneuronopathy in Mouse
Saul A. Mullen, MBBS;
Ingrid E. Scheffer, MBBS, PhD
Arch Neurol. 2009;66(1):21-26.
Voltage-gated sodium channels are critical for membrane excitability. Mutations in the genes coding for these proteins cause diseases related to altered excitability of cardiac or skeletal muscle and neurons. Mutations in the central nervous system–specific voltage-gated sodium channel  1 subunit gene (SCN1A) lead not only to seizure syndromes but also to familial hemiplegic migraine. The epilepsies range from benign febrile seizures to the catastrophic epileptic encephalopathy of Dravet syndrome (severe myoclonic epilepsy of infancy). Recently developed animal models of SCN1A mutants recapitulate the human disease. These models exemplify the potential inherent in translational research to debunk preconceived ideas regarding pathogenesis by showing the cellular substrate of Dravet syndrome to be interneurons rather than excitatory cells. This illustrates the key role that basic science plays in the development of targeted novel therapies and, ultimately, in the prevention of devastating genetic disorders.
Author Affiliations: Epilepsy Research Centre and Department of Medicine, University of Melbourne, Austin Health, Heidelberg, Victoria, Australia (Drs Mullen and Scheffer); and Department of Paediatrics, University of Melbourne, Royal Children's Hospital, Melbourne (Dr Scheffer).
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