Mucociliary clearance of inhaled particles from the tracheobronchial tree is an important defense mechanism of the lung. A failure of this clearance mechanism in disease probably results in retained mucous secretions and a predisposition to pulmonary infection. Circumstantial evidence indicates that airway secretion of ions, water, and mucus is an important factor in determining the rate of mucociliary clearance. Since the normal and abnormal physiology of these important secretory processes is only partially known, my proposal is to study the interrelationship among these processes. In other epithelia, water movement occurs in response to osmotic gradients created by the active transport of ions. Previously, we showed that there is a predominant chloride ion pump directed toward the tracheal lumen and a smaller sodium ion pump facing in the opposite direction. Also, we obtained data that is consistent with Na ion-dependent electrogenic Cl ion secretion in this epithelium. We plan to characterize further ion transport in tracheal epithelium by determining the electrochemical gradients across the cell membranes of individual cells of the epithelium. We will also determine the influx and efflux of Cl ion and Na ion in the epithelium. Furthermore, we propose to develop a technique to measure water movement across dog tracheal epithelium in vitro, and to correlate the ion transpot and the electrical properties of the epithelium with water movement. In the above studies, we will employ acetylcholine, terbutaline, furosemide, and ouabain, as well as varying concentrations of Na ion and Cl ion (and in the water movement studies, Ca2ion in the bathing media to further define these processes.
NIH ExPorter
NIH ExPorter