and specific aims): Current evidence indicates that the alveolar epithelium constitutes a """"""""tight"""""""" epithelial barrier that restricts flow of solutes and water, and actively transports sodium (Na) from air space to blood. The transepithelial resistance (TER) of the alveolar barrier depends on the integrity of the intercellular connections (tight junctions) between its cells, while its capacity for active transport depends primarily on the presence and activity of apical amiloride-sensitive Na channels and basolateral Na pumps (Na+,K+-ATPase) in the plasma membranes of the alveolar epithelial cells (AECs). Due to the complex anatomy and cellular heterogeneity of the lung, however, in vivo and in situ studies are limited in their ability to yield information on specific mechanisms of alveolar epithelial transport at the tissue, cell, and subcellular levels. An in vitro model has been developed in which AECs are grown on permeable supports to form electrically resistive monolayers that vectorially transport solutes and water. These monolayers will be used to pursue the following specific aims: 1) To investigate the long-term regulation of transepithelial transport by specific extracellular factors; 2) to investigate stimulus-specific effects on the membrane processes involved in active Na transport; and 3) to determine the role of stimulus-specific alterations in Na channel and Na+,K+-ATPase gene and protein expression in long-term regulation of active Na transport.
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