Functional voltage-gated sodium channels are expressed in human intestinal epithelial cells

Iris Barshack, Mia Levite, Alon Lang, Ella Fudim, Orit Picard, Shomron Ben Horin, Yehuda Chowers

Research output: Contribution to journalArticlepeer-review

Abstract

Background and Aim: Local anesthetics which preferentially interact with voltage-gated sodium channels (VGSCs) were shown to have a clinical beneficial effect in ulcerative colitis and to regulate the secretion of inflammatory mediators from intestinal epithelial cells. However, expression of VGSCs in epithelial cells was not demonstrated. Herein we assessed whether intestinal epithelial cells express VGSCs. Methods: The expression of VGSCs in normal human colonic tissue and in the TNFα-treated or untreated intestinal epithelial cell line HT-29 was studied by immunofluorescence staining and FACS analysis, Western blot, immunohistochemistry, and RT-PCR using primers specific for several VGSC α subunits. The function of VGSCs was assessed by measuring changes in the membrane potential of the intestinal epithelial cells following incubation with lidocaine, veratridine, or both. Results: HT-29 cells were shown to express the VGSC α protein. mRNA analysis revealed the expression of nine of ten VGSC α isoforms. Immunohistochemical staining of normal colonic tissue confirmed the expression of VGSCs in colonic epithelial cells, smooth muscle cells, and nerves. Lidocaine induced membrane depolarization of HT-29 cells and its effect was blocked by veratridine. Conclusion: Malignant and normal intestinal epithelial cells express functional VGSCs. These molecules may play a role in the regulation of inflammation in gut physiology and pathology.

Original languageEnglish
Pages (from-to)108-117
Number of pages10
JournalDigestion
Volume77
Issue number2
DOIs
StatePublished - Apr 2008

Keywords

  • Intestinal epithelial cells
  • Local anesthetics
  • Voltage-gated sodium channels

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