In many epithelial cells, the rate of sodium reabsorption is governed by the activity of the epithelial sodium channel (ENaC). ENaC activity is governed by a wide variety of physiologic conditions and hormonal influences. The goal of the following research project is to characterize the trafficking of ENaC in renal epithelial cells. Many studies have looked at the regulation of ENaC activity, but it has been found to be very complex and a more detailed understanding is lacking. Our laboratory and others have some data suggesting that there may be differential expression of ENaC subunits in assembly and trafficking. We are proposing a novel approach to study ENaC expression using polarized, hormonally responsive MDCK cells. We will use replication-defective recombinant adenoviruses to express individual ENaC subunits or combinations of subunits in MDCK cells; the advantages of this approach are that it allows us tremendous flexibility in expressing various combinations of channel subunits in controllable levels. We will be using this system to better study the delivery, turnover and recycling of subunits on the apical surface. The data that we will gather will provide an important comparison to previous studies done in oocytes. Together, these data will demonstrate whether ENaC channel composition is fixed or fluid and address the questions of where and how ENaC channel assembly is regulated.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32DK065408-02
Application #
6878037
Study Section
Special Emphasis Panel (ZRG1-F10 (21))
Program Officer
Rankin, Tracy L
Project Start
2003-07-01
Project End
2005-06-30
Budget Start
2004-07-01
Budget End
2005-06-30
Support Year
2
Fiscal Year
2004
Total Cost
$54,352
Indirect Cost
Name
University of Pittsburgh
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213