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Am J Physiol Cell Physiol 284: C1021-C1030, 2003. First published December 18, 2002; doi:10.1152/ajpcell.00149.2002
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Vol. 284, Issue 4, C1021-C1030, April 2003

Inhibitors of glycosphingolipid biosynthesis reduce transepithelial electrical resistance in MDCK I and FRT cells

Lawrence W. Leung1, Ruben G. Contreras2, Catalina Flores-Maldonado2, Marcelino Cereijido2, and Enrique Rodriguez-Boulan1,3

1 Margaret M. Dyson Vision Research Institute, Department of Ophthalmology, and 3 Department of Cell Biology, Weill Medical College of Cornell University, New York, New York 10021; and 2 Department of Physiology, Center for Research and Advanced Studies, 07000 Mexico City DF, Mexico

Madin-Darby canine kidney (MDCK) I and Fisher rat thyroid (FRT) cells exhibit transepithelial electrical resistance (TER) values in excess of 5,000 Omega  · cm2. When these cells were incubated in the presence of various inhibitors of sphingolipid biosynthesis, a >5-fold reduction of TER was observed without changes in the gate function for uncharged solutes or the fence function for apically applied fluorescent lipids. The localization of ZO-1 and occludin was not altered between control and inhibitor-treated cells, indicating that the tight junction was still intact. Furthermore, the complexity of tight junction strands, analyzed by freeze-fracture microscopy, was not reduced. Once the inhibitor was removed and the cells were allowed to synthesize sphingolipids, a gradual recovery of the TER was observed. Interestingly, these inhibitors did not attenuate the TER of MDCK II cells, a cell line that typically exhibits values below 800 Omega  · cm2. These results suggest that glycosphingolipids play a role in regulating the electrical properties of epithelial cells.

lipid microdomains; caveolin; claudin; occludin


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M. Cereijido, R. G. Contreras, and L. Shoshani
Cell Adhesion, Polarity, and Epithelia in the Dawn of Metazoans
Physiol Rev, October 1, 2004; 84(4): 1229 - 1262.
[Abstract] [Full Text] [PDF]


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