Abnormal bicarbonate secretion has long been recognized as a key component of cystic fibrosis (CF) pancreatic dysfunction, but has only recently been investigated as a component of CF lung disease. The submucoal glands of the lungs are responsible for secretion of a complex airway surface liquid (ASL) that lines the airway epithelium and plays a significant role in mucociliary clearance. The serous cell is the predominant cell type of the submucosal gland and the predominant site of cystic fibrosis transmembrane conductance regulator (CFTR) expression. The Calu-3 cell, an immortalized serous cell line, is therefore a good model for the study of the physiology of ASL production and regulation. This proposal is divided into two complementary aims.
The first aim i s to use microelectrode measurements to establish the transport physiology of bicarbonate entry on a sodium-bicarbonate cotransporter, and then to use short, inhibiting RNA technology to determine the identity of the sodium-bicarbonate cotransporter.
The second aim i s to use short, inhibitory RNA technology to knock-down CFTR and to use these knock-down cell lines in Ussing chamber experiments and microelectrode experiments to test the hypothesis that CFTR is the apical bicarbonate channel.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HL074575-01
Application #
6692087
Study Section
Special Emphasis Panel (ZRG1-F10 (20))
Program Officer
Rothgeb, Ann E
Project Start
2003-08-12
Project End
2006-08-11
Budget Start
2003-08-12
Budget End
2004-08-11
Support Year
1
Fiscal Year
2003
Total Cost
$51,904
Indirect Cost
Name
Children's Hosp Pittsburgh/Upmc Health Sys
Department
Type
DUNS #
044304145
City
Pittsburgh
State
PA
Country
United States
Zip Code
15224
Kreindler, James L; Jackson, Alan D; Kemp, Philip A et al. (2005) Inhibition of chloride secretion in human bronchial epithelial cells by cigarette smoke extract. Am J Physiol Lung Cell Mol Physiol 288:L894-902