Document Detail


Functional voltage-gated sodium channels are expressed in human intestinal epithelial cells.
MedLine Citation:
PMID:  18391489     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 TNFalpha-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 alpha 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 alpha protein. mRNA analysis revealed the expression of nine of ten VGSC alpha 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.
Authors:
Iris Barshack; Mia Levite; Alon Lang; Ella Fudim; Orit Picard; Shomron Ben Horin; Yehuda Chowers
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-04-07
Journal Detail:
Title:  Digestion     Volume:  77     ISSN:  1421-9867     ISO Abbreviation:  Digestion     Publication Date:  2008  
Date Detail:
Created Date:  2008-04-17     Completed Date:  2008-06-13     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0150472     Medline TA:  Digestion     Country:  Switzerland    
Other Details:
Languages:  eng     Pagination:  108-17     Citation Subset:  IM    
Copyright Information:
Copyright 2008 S. Karger AG, Basel.
Affiliation:
Department of Pathology, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
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MeSH Terms
Descriptor/Qualifier:
Anesthetics, Local / pharmacology
Colon / metabolism
HT29 Cells
Humans
Intestinal Mucosa / drug effects,  metabolism*
Lidocaine / pharmacology
Membrane Potentials / drug effects
Sodium Channels / drug effects,  metabolism*
Chemical
Reg. No./Substance:
0/Anesthetics, Local; 0/Sodium Channels; 137-58-6/Lidocaine

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