Variability in renal tubular flow rates subject tubular epithelial cells to changes in shear stress and hydrostatic pressure that ultimately affects cellular function. The distal nephron, and specifically the cortical collecting duct (CCD), is comprised of 2 major cell types: Na-absorbing principal cells (70%) and acid-base transporting intercalated cells (30%). Principal cells possess apical epithelial Na channels (ENaCs), which have a key role in transepithelial Na absorption. Acid-base transport by intercalated cells is mediated by apical anion exchangers and proton pumps localized to beta-and alpha-intercalated cells, respectively. Rabbit CCDs respond to an increase in flow with an increase in Na absorption as well as a reduction in bicarbonate secretion. This application will address mechanisms underlying flow-dependence of ENaC activation, and thus extend studies begun in the current funding period, and initiate an investigation directed at exploring mechanisms underlying flow-regulation of proton and bicarbonate transport. Proposed studies will utilize CCDs, cultured epithelial cells and Xenopus oocytes to determine mechanisms by which flow increases ENaC open probability. Studies in rabbit CCDs will address mechanisms by which flow reduces net bicarbonate secretion. These proposed studies should provide new information regarding the regulation of Na and acid/base transport in the CCD.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Method to Extend Research in Time (MERIT) Award (R37)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-RUS-G (02))
Program Officer
Ketchum, Christian J
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pittsburgh
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Carrisoza-Gaytán, Rolando; Wang, Lijun; Schreck, Carlos et al. (2017) The mechanosensitive BK?/?1 channel localizes to cilia of principal cells in rabbit cortical collecting duct (CCD). Am J Physiol Renal Physiol 312:F143-F156
Kashlan, Ossama B; Kinlough, Carol L; Myerburg, Michael M et al. (2017) N-linked Glycans are Required on Epithelial Na+ Channel Subunits for Maturation and Surface Expression. Am J Physiol Renal Physiol :ajprenal.00195.2017
Buck, Teresa M; Jordahl, Alexa S; Yates, Megan E et al. (2017) Interactions between intersubunit transmembrane domains regulate the chaperone-dependent degradation of an oligomeric membrane protein. Biochem J 474:357-376
Shi, Shujie; Buck, Teresa M; Kinlough, Carol L et al. (2017) Regulation of the epithelial Na+ channel by paraoxonase-2. J Biol Chem 292:15927-15938
Mukherjee, Anindit; Wang, Zhijian; Kinlough, Carol L et al. (2017) Specific Palmitoyltransferases Associate with and Activate the Epithelial Sodium Channel. J Biol Chem 292:4152-4163
Ray, Evan C; Chen, Jingxin; Kelly, Tanika N et al. (2016) Human epithelial Na+ channel missense variants identified in the GenSalt study alter channel activity. Am J Physiol Renal Physiol 311:F908-F914
Carrisoza-Gaytan, Rolando; Carattino, Marcelo D; Kleyman, Thomas R et al. (2016) An unexpected journey: conceptual evolution of mechanoregulated potassium transport in the distal nephron. Am J Physiol Cell Physiol 310:C243-59
Shi, Shujie; Luke, Cliff J; Miedel, Mark T et al. (2016) Activation of the Caenorhabditis elegans Degenerin Channel by Shear Stress Requires the MEC-10 Subunit. J Biol Chem 291:14012-22
Webb, Tennille N; Carrisoza-Gaytan, Rolando; Montalbetti, Nicolas et al. (2016) Cell-specific regulation of L-WNK1 by dietary K. Am J Physiol Renal Physiol 310:F15-26
Kashlan, Ossama B; Blobner, Brandon M; Zuzek, Zachary et al. (2015) Na+ inhibits the epithelial Na+ channel by binding to a site in an extracellular acidic cleft. J Biol Chem 290:568-76

Showing the most recent 10 out of 40 publications