Amiloride-sensitive epithelial sodium channels (ENaC) play an important role in lung sodium transport. Sodium transport is closely regulated to maintain an appropriate fluid layer on the alveolar surface. Both alveolar type I and II cells have several different sodium-permeable channels in their apical membranes that play a role in normal lung physiology and pathophysiology. In many epithelial tissues, ENaC is formed from three subunit proteins: alpha, beta, and gamma ENaC. Part of the diversity of sodium-permeable channels in lung arises from assembling different combinations of these subunits to form channels with different biophysical properties and different mechanisms for regulation. Thus, lung epithelium has enormous flexibility to alter the magnitude of salt and water transport. In lung, ENaC is regulated by many transmitter and hormonal agents. Regulation depends upon the type of sodium channel but involves controlling the number of apical channels and/or the activity of individual channels.

Efficient gas exchange in the lungs depends on regulation of the amount of fluid in the thin (average 0.2 m) liquid layer lining the alveolar epithelium. Fluid fluxes are regulated by ion transport across the alveolar epithelium, which is composed of alveolar type I (TI) and type II (TII) cells. The accepted paradigm has been that TII cells, which cover <5% of the internal surface area of the lung, transport Na ؉ and Cl ؊ and that TI cells, which cover >95% of the surface area, provide a route for water absorption. Here we present data that TI cells contain functional epithelial Na ؉ channels (ENaC), pimozide-sensitive cation channels, K ؉ channels, and the cystic fibrosis transmembrane regulator. TII cells contain ENaC and cystic fibrosis transmembrane regulator, but few pimozide-sensitive cation channels. These findings lead to a revised paradigm of ion and water transport in the lung in which (i) Na ؉ and Cl ؊ transport occurs across the entire alveolar epithelium (TI and TII cells) rather than only across TII cells; and (ii) by virtue of their very large surface area, TI cells are responsible for the bulk of transepithelial Na ؉ transport in the lung.S hortly before birth, the fetal lung converts from fluid secretion to fluid reabsorption. After birth, efficient gas exchange depends on regulation of the amount of fluid in the thin (average, 0.2 m) liquid layer lining the alveolar epithelium (1). Alveolar flooding resulting from cardiogenic pulmonary edema or acute lung injury impairs gas diffusion across the air͞blood barrier; an increase in alveolar fluid clearance restores a normal air͞blood barrier. Alveolar fluid transport from alveolar to interstitial spaces, driven by active Na ϩ transport across the alveolar epithelium (2), can be inhibited either by the addition of amiloride, a Na ϩ channel inhibitor, to the alveolar space, or ouabain, a Na ϩ ,K ϩ -ATPase inhibitor, to the vascular bed (3), suggesting that the alveolar epithelium is the major site of Na ϩ transport and fluid absorption in the adult lung.The alveolar epithelium, which covers Ͼ99% of the large internal surface area of the lung (4), is composed of two cell types, alveolar type I (TI) and type II (TII) cells. TII cells, which cover 2-5% of the internal surface area of the lung, are cuboidal cells that synthesize and secrete pulmonary surfactant. TII cells contain ion channels, including the amiloride-sensitive epithelial Na ϩ channel (ENaC) (5), Na ϩ ,K ϩ -ATPase (3) and the cystic fibrosis transmembrane regulator (CFTR) (6). TI cells are large squamous cells whose thin cytoplasmic extensions cover Ͼ95% of the internal surface area of the lung (7). TI cells express aquaporin 5, a water channel (8), and have the highest known osmotic water permeability of any mammalian cell type (9). The observations that TII cells contain ion channels and TI cells express aquaporins led to the paradigm that TII cells govern alveolar fluid balance by regulating Na ϩ transport in the lungs, whereas TI cells merely provide a route for passive water absorpti...

This study provides evidence that decreased expression of the desmosomal cadherin desmocollin-2 enhances intestinal epithelial cell proliferation and promotes tumor formation via an Akt/β-catenin pathway.

The alveolar surface of the lung is lined by alveolar type 1 (AT1) and type 2 (AT2) cells. Using single channel patch clamp analysis in lung slice preparations, we are able to uniquely study AT1 and AT2 cells separately from intact lung. We report for the first time the Na

The lung is dynamically remodeled in response to injury, which alters extracellular matrix composition, and can lead to either healthy or impaired lung regeneration. To determine how changes in extracellular matrix can influence alveolar epithelial barrier function, we examined the expression and function of tight junction proteins by rat alveolar epithelial type II cells cultured on one of three different matrix components: type I collagen or fibronectin, matrix glycoproteins which are highly expressed in injured lungs, or laminin, a basement membrane matrix component. Of note, alveolar epithelial cells cultured for 2 days on fibronectin formed high-resistance barriers and showed continuous claudin-3 and claudin-18 localization to the plasma membrane, as opposed to cells cultured on either type I collagen or laminin, which had low resistance monolayers and had areas of cell-cell contact that were claudin deficient. The barrier formed by cells cultured on fibronectin also had preferential permeability to chloride as compared with sodium. Regardless of the initial matrix composition, alveolar epithelial cells cultured for 5 days formed high-resistance barriers, which correlated with increased claudin-18 localization to the plasma membrane and an increase in zonula occludens-1. Day 5 cells on laminin had significantly higher resistance than cells on either fibronectin or type I collagen. Thus, although alveolar epithelial cells on fibronectin formed rapid barriers, it was at the expense of producing an optimized barrier.