Ouabain modulates epithelial cell tight junction

• Published in: Proceedings of the National Academy of Sciences - PNAS 2010-06, Vol.107 (25), p.11387-11392
• Main Authors: Larre, Isabel, Lazaro, Amparo, Contreras, Ruben G., Balda, Maria S., Matter, Karl, Flores-Maldonado, Catalina, Ponce, Arturo, Flores-Benitez, David, Rincon-Heredia, Ruth, Padilla-Benavides, Teresita, Castillo, Aída, Shoshani, Liora, Cereijido, Marcelino, Latorre, Ramón
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis; Biological Sciences; Cell adhesion; Cell membranes; Cellular biology; Chemical compounds; Dextrans; Dextrans - chemistry; Dogs; Dose-Response Relationship, Drug; Enzyme Inhibitors - pharmacology; Epithelial cells; Epithelial Cells - cytology; Epithelial Cells - drug effects; Extracellular Signal-Regulated MAP Kinases - metabolism; Ions; Kidney cells; Membranes; Models, Biological; Neurons; Ouabain - pharmacology; Pharmaceuticals; Physiological regulation; Plasma; Potassium - chemistry; Protein-Tyrosine Kinases - metabolism; Pumps; Signal Transduction; Sodium-Potassium-Exchanging ATPase - metabolism; src-Family Kinases; Tight junctions; Tight Junctions - drug effects
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.1000500107

Epithelial cells treated with high concentrations of ouabain (e.g., 1 μM) retrieve molecules involved in cell contacts from the plasma membrane and detach from one another and their substrates. On the basis of this observation, we suggested that ouabain might also modulate cell contacts at low, nontoxic levels (10 or 50 nM). To test this possibility, we analyzed its effect on a particular type of cell—cell contact: the tight junction (TJ). We demonstrate that at concentrations that neither inhibit K⁺ pumping nor disturb the K⁺ balance of the cell, ouabain modulates the degree of sealing of the TJ as measured by transepithelial electrical resistance (TER) and the flux of neutral 3 kDa dextran (J DEX ). This modulation is accompanied by changes in the levels and distribution patterns of claudins 1, 2, and 4. Interestingly, changes in TER, J DEX , and claudins behavior are mediated through signal pathways containing ERK1/2 and c-Src, which have distinct effects on each physiological parameter and claudin type. These observations support the theory that at low concentrations, ouabain acts as a modulator of cell—cell contacts.