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The firing and response properties of mammalian central neurons are highly variable, reflecting differences in the Nav (and other) channels expressed and the synaptic connectivity of the circuits in which the cells participate. Transient (I\n                    <jats:sub>NaT<\/jats:sub>\n                    ), persistent (I\n                    <jats:sub>NaP<\/jats:sub>\n                    ) and resurgent (I\n                    <jats:sub>NaR<\/jats:sub>\n                    ) Nav current components have been distinguished, and considerable progress has been made in defining their roles in regulating the firing properties of central neurons and the mechanisms underlying their generation. In addition, it is well established that native neuronal Nav channels function in macromolecular complexes, comprising a pore\u2010forming \u03b1 subunit assembled with multiple accessory\/auxiliary proteins that influence channel expression, localization and biophysical properties. In mature central neurons, the Nav1.1, Nav1.2 and Nav1.6 \u03b1 subunits are differentially expressed, together with one or more of the Nav beta (Nav\u03b21\u20104), intracellular fibroblast growth factor (iFGF11\u201314), ankyrin (Ankyrin\u2010B, \u2010G, \u2010R) and other auxiliary proteins, generating Nav channels with diverse cell\u2010type\u2010 and circuit\u2010specific expression patterns, subcellular distributions, gating properties, and physiological roles. Variants in the genes encoding these Nav \u03b1 subunits (\n                    <jats:italic>SCN1A<\/jats:italic>\n                    ,\n                    <jats:italic>SCN2A<\/jats:italic>\n                    ,\n                    <jats:italic>SCN8A<\/jats:italic>\n                    ), as well as Nav\u03b21 (\n                    <jats:italic>SCN1B<\/jats:italic>\n                    ), iFGFs (\n                    <jats:italic>FGF12<\/jats:italic>\n                    ,\n                    <jats:italic>FGF13<\/jats:italic>\n                    ,\n                    <jats:italic>FGF14<\/jats:italic>\n                    ), ankyrins (\n                    <jats:italic>ANK1<\/jats:italic>\n                    ,\n                    <jats:italic>ANK2<\/jats:italic>\n                    ,\n                    <jats:italic>ANK3<\/jats:italic>\n                    ), and other Nav channel auxiliary and interacting proteins, have been linked to several congenital neurological disorders, including epilepsy and ataxia, as well as to neurodevelopmental, neurodegenerative and psychiatric diseases.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70709-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1113\/jp289491","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T17:35:44Z","timestamp":1785951344000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Molecular determinants of functional voltage\u2010gated sodium (Nav) channel diversity in mammalian central neurons"],"prefix":"10.1113","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5908-9044","authenticated-orcid":false,"given":"Joseph L.","family":"Ransdell","sequence":"first","affiliation":[{"name":"Department of Biology Miami University  Oxford Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8334-8499","authenticated-orcid":false,"given":"Jeanne M.","family":"Nerbonne","sequence":"additional","affiliation":[{"name":"Department of Developmental Biology Washington University Medical School  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,5]]},"reference":[{"issue":"5","key":"e_1_2_2_2_1","doi-asserted-by":"crossref","first-page":"2831","DOI":"10.1152\/jn.00261.2004","article-title":"Resurgent Na currents in four classes of neurons of the cerebellum","volume":"92","author":"Afshari F. 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