{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:54:02Z","timestamp":1791190442070,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,7,2]],"date-time":"2013-07-02T00:00:00Z","timestamp":1372723200000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2013,7]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Neuronal channelopathies cause brain disorders, including epilepsy, migraine, and ataxia. Despite the development of mouse models, pathophysiological mechanisms for these disorders remain uncertain. One particularly devastating channelopathy is Dravet syndrome (DS), a severe childhood epilepsy typically caused by de novo dominant mutations in the <jats:italic>SCN1A<\/jats:italic> gene encoding the voltage\u2010gated sodium channel Na<jats:sub>v<\/jats:sub>1.1. Heterologous expression of mutant channels suggests loss of function, raising the quandary of how loss of sodium channels underlying action potentials produces hyperexcitability. Mouse model studies suggest that decreased Na<jats:sub>v<\/jats:sub>1.1 function in interneurons causes disinhibition. We aim to determine how mutant <jats:italic>SCN1A<\/jats:italic> affects human neurons using the induced pluripotent stem cell (iPSC) method to generate patient\u2010specific neurons.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here we derive forebrain\u2010like pyramidal\u2010 and bipolar\u2010shaped neurons from 2 DS subjects and 3 human controls by iPSC reprogramming of fibroblasts. DS and control iPSC\u2010derived neurons are compared using whole\u2010cell patch clamp recordings. Sodium current density and intrinsic neuronal excitability are examined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Neural progenitors from DS and human control iPSCs display a forebrain identity and differentiate into bipolar\u2010 and pyramidal\u2010shaped neurons. DS patient\u2010derived neurons show increased sodium currents in both bipolar\u2010 and pyramidal\u2010shaped neurons. Consistent with increased sodium currents, both types of patient\u2010derived neurons show spontaneous bursting and other evidence of hyperexcitability. Sodium channel transcripts are not elevated, consistent with a post\u2010translational mechanism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>These data demonstrate that epilepsy patient\u2013specific iPSC\u2010derived neurons are useful for modeling epileptic\u2010like hyperactivity. Our findings reveal a previously unrecognized cell\u2010autonomous epilepsy mechanism potentially underlying DS, and offer a platform for screening new antiepileptic therapies. Ann Neurol 2013;74:128\u2013139<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.23897","type":"journal-article","created":{"date-parts":[[2013,3,28]],"date-time":"2013-03-28T10:09:14Z","timestamp":1364465354000},"page":"128-139","source":"Crossref","is-referenced-by-count":217,"title":["Dravet syndrome patient\u2010derived neurons suggest a novel epilepsy mechanism"],"prefix":"10.1002","volume":"74","author":[{"given":"Yu","family":"Liu","sequence":"first","affiliation":[{"name":"Departments of Neurology University of Michigan Medical Center Ann Arbor MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis F.","family":"Lopez\u2010Santiago","sequence":"additional","affiliation":[{"name":"Pharmacology University of Michigan Medical Center Ann Arbor MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukun","family":"Yuan","sequence":"additional","affiliation":[{"name":"Pharmacology University of Michigan Medical Center Ann Arbor 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