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Sodium channel NaV1.3 is important for enterochromaffin cell excitability and serotonin release.

Publication ,  Journal Article
Strege, PR; Knutson, K; Eggers, SJ; Li, JH; Wang, F; Linden, D; Szurszewski, JH; Milescu, L; Leiter, AB; Farrugia, G; Beyder, A
Published in: Sci Rep
November 15, 2017

In 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.

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Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

November 15, 2017

Volume

7

Issue

1

Start / End Page

15650

Location

England

Related Subject Headings

  • Voltage-Gated Sodium Channels
  • Sodium Channel Blockers
  • Serotonin
  • Primary Cell Culture
  • NAV1.3 Voltage-Gated Sodium Channel
  • Mice
  • Humans
  • Gene Expression Regulation, Developmental
  • Enteroendocrine Cells
  • Enterochromaffin Cells
 

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Strege, P. R., Knutson, K., Eggers, S. J., Li, J. H., Wang, F., Linden, D., … Beyder, A. (2017). Sodium channel NaV1.3 is important for enterochromaffin cell excitability and serotonin release. Sci Rep, 7(1), 15650. https://doi.org/10.1038/s41598-017-15834-3
Strege, Peter R., Kaitlyn Knutson, Samuel J. Eggers, Joyce H. Li, Fan Wang, David Linden, Joseph H. Szurszewski, et al. “Sodium channel NaV1.3 is important for enterochromaffin cell excitability and serotonin release.Sci Rep 7, no. 1 (November 15, 2017): 15650. https://doi.org/10.1038/s41598-017-15834-3.
Strege PR, Knutson K, Eggers SJ, Li JH, Wang F, Linden D, et al. Sodium channel NaV1.3 is important for enterochromaffin cell excitability and serotonin release. Sci Rep. 2017 Nov 15;7(1):15650.
Strege, Peter R., et al. “Sodium channel NaV1.3 is important for enterochromaffin cell excitability and serotonin release.Sci Rep, vol. 7, no. 1, Nov. 2017, p. 15650. Pubmed, doi:10.1038/s41598-017-15834-3.
Strege PR, Knutson K, Eggers SJ, Li JH, Wang F, Linden D, Szurszewski JH, Milescu L, Leiter AB, Farrugia G, Beyder A. Sodium channel NaV1.3 is important for enterochromaffin cell excitability and serotonin release. Sci Rep. 2017 Nov 15;7(1):15650.

Published In

Sci Rep

DOI

EISSN

2045-2322

Publication Date

November 15, 2017

Volume

7

Issue

1

Start / End Page

15650

Location

England

Related Subject Headings

  • Voltage-Gated Sodium Channels
  • Sodium Channel Blockers
  • Serotonin
  • Primary Cell Culture
  • NAV1.3 Voltage-Gated Sodium Channel
  • Mice
  • Humans
  • Gene Expression Regulation, Developmental
  • Enteroendocrine Cells
  • Enterochromaffin Cells