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


CONCLUSIONS
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.
Barshack
Iris
I
Department of Pathology, Chaim Sheba Medical Center, Tel-Hashomer, Israel.
Levite
Mia
M
Lang
Alon
A
Fudim
Ella
E
Picard
Orit
O
Ben Horin
Shomron
S
Chowers
Yehuda
Y
D000779:Anesthetics, Local / Q000494:pharmacology; D003106:Colon / Q000378:metabolism; D019073:HT29 Cells; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism*; D008012:Lidocaine / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*
D000779:Anesthetics, Local; D015222:Sodium Channels; D008012:Lidocaine