Exocytosis in pulmonary alveolar type II cells

Alveoli of the lung are the site of gas exchange between air and blood. The pulmonary alveolar epithelium consists of two cell types: type I cells and type II cells. Type II cells account for only 10% of the alveolar surface. Nevertheless, they control alveolar distensibility (the ability to breath) and fluid homeostasis in various ways. Their main functions are: - secretion of surfactant via exocytosis of surfactant stored in "lamellar bodies" (LBs) - active electrolyte and fluid transport The most important goal of surfactant secretion is to facilitate inspiration by reducing the surface tension at the air liquid interface, its dysfunction causes respiratory distress syndrome. Active electrolyte and fluid transport is achieved by pumps and ion channels and helps to prevent edema of the lung. Despite decades of intensive research, experimental models in which both, ion currents and secretion in type II cells, can be simultaneously assessed under nearly physiological (i.e. well-differentiated) conditions are still lacking. Although structural and functional information about channels involved in transepithelial NaCl transport is continuously growing, we know very little about ion channels and their involvement in the exocytotic process of surfactant. Based on many previous investigations and recently developed methods to study single exocytotic events, we plan to investigate the relationship between ion channel and exocytotic activity in type II cells, particularly with regard to Ca2+ entry and its control. Furthermore, it is our goal to identify molecular components of the exocytotic machinery which control the final steps of Ca2+-induced LB fusion and fusion pore expansion. These studies should yield information about the regulation of secretion on a cellular / molecular level in well- differentiated type II cells. In addition to the relevance of these studies for pulmonary physiology and pathophysiology, some general aspects of the exocytotic process, such as mechanisms of membrane fusion and fusion pore expansion, will be addressed.