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To further understand the low current density observed in human Na\n            <jats:sub>V<\/jats:sub>\n            1.9, we created chimeras with Na\n            <jats:sub>V<\/jats:sub>\n            1.5 and identified a role for the C-tail\u2014specifically the IQ motif and EF-hand\u2014in regulating current densities, likely due to a weak affinity for calmodulin. Isothermal titration calorimetry experiments indicated that, unlike other Na\n            <jats:sub>V<\/jats:sub>\n            channel subtypes, calmodulin binding to the C-tail is likely too weak to occur under physiological conditions. Markedly, the pre-IQ region did not influence channel expression but was responsible for conferring the characteristic depolarized voltage dependency of inactivation of Na\n            <jats:sub>V<\/jats:sub>\n            1.9. Our findings provide insights into the unique gating mechanisms of Na\n            <jats:sub>V<\/jats:sub>\n            1.9 and demonstrate the robustness of this platform for structure-function studies.\n          <\/jats:p>","DOI":"10.1126\/sciadv.adt9799","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T17:58:47Z","timestamp":1748455127000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":3,"title":["A robust expression system reveals distinct gating mechanisms and calmodulin regulation of Na\n            <sub>V<\/sub>\n            1.9 channels"],"prefix":"10.1126","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0058-104X","authenticated-orcid":true,"given":"Margaux","family":"Theys","sequence":"first","affiliation":[{"name":"Molecular Physiology and Neurophysics group, Department of Basic and Applied Medical Sciences, Faculty of Medicine and Health Sciences, University 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