Acute regulation of tight junction ion selectivity in human airway epithelia

• Published in: Proceedings of the National Academy of Sciences - PNAS 2009-03, Vol.106 (9), p.3591-3596
• Main Authors: Flynn, Andrea N, Itani, Omar A, Moninger, Thomas O, Welsh, Michael J
• Format: Article
• Language: English
• Subjects: Biological Sciences; Biological Transport; Cell lines; Cells; Cells, Cultured; Electrolytes; Epithelial cells; Epithelial Cells - metabolism; Epithelial Cells - ultrastructure; Extracellular space; Histamine - metabolism; Histamines; Humans; Ion transport; Ions; Ions - metabolism; Lanthanum - metabolism; Mast cells; Membrane Proteins - metabolism; Microscopy, Electron, Transmission; Physiological regulation; Protein Isoforms - metabolism; Receptors; Receptors, Histamine - metabolism; Respiratory system; Respiratory System - metabolism; Respiratory System - ultrastructure; Sodium - metabolism; Studies; Tight junctions; Tight Junctions - metabolism; Tight Junctions - ultrastructure; Tissues
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.0813393106

Electrolyte transport through and between airway epithelial cells controls the quantity and composition of the overlying liquid. Many studies have shown acute regulation of transcellular ion transport in airway epithelia. However, whether ion transport through tight junctions can also be acutely regulated is poorly understood both in airway and other epithelia. To investigate the paracellular pathway, we used primary cultures of differentiated human airway epithelia and assessed expression of claudins, the primary determinants of paracellular permeability, and measured transepithelial electrical properties, ion fluxes, and La³⁺ movement. Like many other tissues, airway epithelia expressed multiple claudins. Moreover, different cell types in the epithelium expressed the same pattern of claudins. To evaluate tight junction regulation, we examined the response to histamine, an acute regulator of airway function. Histamine stimulated a rapid and transient increase in the paracellular Na⁺ conductance, with a smaller increase in Cl⁻ conductance. The increase was mediated by histamine H₁ receptors and depended on an increase in intracellular Ca²⁺ concentration. These results suggest that ion flow through the paracellular pathway can be acutely regulated. Such regulation could facilitate coupling of the passive flow of counter ions to active transcellular transport, thereby controlling net transepithelial salt and water transport.