The lungs are kept rom collapsing by a material called surfactant, which is produced and secreted into the airspaces of the lung by one of the cell types which line the airspaces, type II alveolar epithelial cells. Abnormal production, secretion or reuptake of surfactant by type II cells results in diseases such as pulmonary alveolar proteinosis and infant respiratory distress syndrome. Despite the clinical importance of surfactant, little is known about the regulatory mechanisms involved. In the past decade, technical advances have been made which make this proposal possible. First, techniques for isolating and culturing type II cells now permit reliable in vitro studies of surfactant metabolism. Second, the patch clamp technique has enabled electrical recording from small cells such as type II cells. In this project, these techniques will be applied together to characterize the ion channels in rat type II cells, and to determine their role in the production and secretion of surfactant. The patch clamp technique will be used to discover what types of ion channels are present in the plasma membranes of type II cells, to determine the properties of these ion channels, and the numbers of ion channels per cell. Several approaches will be taken to learn what physiological functions the ion channels perform. (1) Comparing the ion channels in type II cells actively secreting surfactant with those in cells that are not may provide clues to which ion channels are involved. (2) Drugs and physiological modulators of surfactant production and secretion will be tested for possible effects on ion channels. (3) Specific ion channel blocking agents will be tested to see whether blocking a given ion channel inhibits surfactant production or secretion. The knowledge gained from this project may eventually enable rational pharmacological intervention in disease conditions exhibiting abnormal surfactant turnover.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL037500-05
Application #
3353209
Study Section
Pathology A Study Section (PTHA)
Project Start
1987-02-01
Project End
1994-01-31
Budget Start
1991-02-01
Budget End
1994-01-31
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost
Name
Rush University Medical Center
Department
Type
DUNS #
City
Chicago
State
IL
Country
United States
Zip Code
60612
DeCoursey, T E; Cherny, V V (1998) Temperature dependence of voltage-gated H+ currents in human neutrophils, rat alveolar epithelial cells, and mammalian phagocytes. J Gen Physiol 112:503-22
Kim, S Y; Silver, M R; DeCoursey, T E (1996) Ion channels in human THP-1 monocytes. J Membr Biol 152:117-30
DeCoursey, T E (1995) Mechanism of K+ channel block by verapamil and related compounds in rat alveolar epithelial cells. J Gen Physiol 106:745-79
Pennefather, P S; DeCoursey, T E (1994) A scheme to account for the effects of Rb+ and K+ on inward rectifier K channels of bovine artery endothelial cells. J Gen Physiol 103:549-81
DeCoursey, T E; Cherny, V V (1994) Na(+)-H+ antiport detected through hydrogen ion currents in rat alveolar epithelial cells and human neutrophils. J Gen Physiol 103:755-85
Silver, M R; Shapiro, M S; DeCoursey, T E (1994) Effects of external Rb+ on inward rectifier K+ channels of bovine pulmonary artery endothelial cells. J Gen Physiol 103:519-48
DeCoursey, T E (1991) Hydrogen ion currents in rat alveolar epithelial cells. Biophys J 60:1243-53
Shapiro, M S; DeCoursey, T E (1991) Permeant ion effects on the gating kinetics of the type L potassium channel in mouse lymphocytes. J Gen Physiol 97:1251-78
Shapiro, M S; DeCoursey, T E (1991) Selectivity and gating of the type L potassium channel in mouse lymphocytes. J Gen Physiol 97:1227-50
Jacobs, E R; DeCoursey, T E (1990) Mechanisms of potassium channel block in rat alveolar epithelial cells. J Pharmacol Exp Ther 255:459-72

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