Strege, Peter R.Knutson, KaitlynEggers, Samuel J.Li, Hui JoyceWang, FanLinden, DavidSzurszewski, Joseph H.Milescu, LorinLeiter, Andrew B.Farrugia, GianricoBeyder, Arthur2022-08-232022-08-232017-11-152018-03-22<p>Sci Rep. 2017 Nov 15;7(1):15650. doi: 10.1038/s41598-017-15834-3. <a href="https://doi.org/10.1038/s41598-017-15834-3">Link to article on publisher's site</a></p>2045-2322 (Linking)10.1038/s41598-017-15834-329142310https://hdl.handle.net/20.500.14038/40505In the gastrointestinal (GI) epithelium, enterochromaffin (EC) cells are enteroendocrine cells responsible for producing > 90% of the body's serotonin (5-hydroxytryptamine, 5-HT). However, the molecular mechanisms of EC cell function are poorly understood. Here, we found that EC cells in mouse primary cultures fired spontaneous bursts of action potentials. We examined the repertoire of voltage-gated sodium channels (NaV) in fluorescence-sorted mouse EC cells and found that Scn3a was highly expressed. Scn3a-encoded NaV1.3 was specifically and densely expressed at the basal side of both human and mouse EC cells. Using electrophysiology, we found that EC cells expressed robust NaV1.3 currents, as determined by their biophysical and pharmacologic properties. NaV1.3 was not only critical for generating action potentials in EC cells, but it was also important for regulating 5-HT release by these cells. Therefore, EC cells use Scn3a-encoded voltage-gated sodium channel NaV1.3 for electrical excitability and 5-HT release. NaV1.3-dependent electrical excitability and its contribution to 5-HT release is a novel mechanism of EC cell function.en-USCopyright © The Author(s) 2017. Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.http://creativecommons.org/licenses/by/4.0/Gastrointestinal systemJejunumBiological FactorsCell BiologyCellsCellular and Molecular PhysiologyDigestive SystemHeterocyclic CompoundsInorganic ChemicalsOrganic ChemicalsJournal Articlehttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=4320&amp;context=oapubs&amp;unstamped=1https://escholarship.umassmed.edu/oapubs/330911825454oapubs/3309