Macula densa cells serve in the transmission of information from tubular fluid to vascular elements through the tubuloglomerular feedback mechanism (TGF). Changes in luminal fluid [NaCl] are sufficient to activate the feedback pathway resulting in information flow from macula densa cells through the mesangial cell field and to the afferent arteriole. At the afferent arteriole, TGF signals result in alterations in membrane potential and changes in cytosolic calcium concentration ([Ca2+]i) through voltage dependent calcium channels. Our previous studies have focused on defining transport systems that operate at the macula densa since understanding these transport pathways should provide substantial insights into the TGF signaling process. With the use of microelectrodes, patch clamp techniques and fluorescence microscopy we have established the existence of apical Na:2Cl:K cotransport, Na:H exchange, K+ channel activity and a predominate CI- conductive pathway at the basolateral membrane. The purpose of these studies is to further our understanding of macula densa transport pathways and how these pathways may contribute to the generation of TGF signals using isolated perfused thick ascending limbs with attached glomeruli from rabbit kidney.
The specific aims of this project are to: I) further characterize and examine the regulation of the major transport pathways located at the apical and basolateral membranes of macula densa cells; 2) determine the effects of intracellular messenger systems and physiological regulators of TGF including angiotensin Il, nitric oxide, thromboxane and adenosine on overall macula densa NaCI transport and membrane potential and 3) correlate changes in macula densa membrane potential, NaCI transport and intracellular messenger systems with TGF mediated alterations in afferent arteriole membrane potential and [Ca2+]i. These studies should provide important new insights into the generation and transmission of tubuloglomerular feedback signals from macula densa cells to arteriolar contractile elements.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG4-GMB (04))
Program Officer
Scherbenske, M James
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Alabama Birmingham
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Sas, Kelli M; Yin, Hong; Fitzgibbon, Wayne R et al. (2015) Hyperglycemia in the absence of cilia accelerates cystogenesis and induces renal damage. Am J Physiol Renal Physiol 309:F79-87
Gilley, Sandra K; Stenbit, Antine E; Pasek, Raymond C et al. (2014) Deletion of airway cilia results in noninflammatory bronchiectasis and hyperreactive airways. Am J Physiol Lung Cell Mol Physiol 306:L162-9
Beck Gooz, Monika; Maldonado, Eduardo N; Dang, Yujing et al. (2014) ADAM17 promotes proliferation of collecting duct kidney epithelial cells through ERK activation and increased glycolysis in polycystic kidney disease. Am J Physiol Renal Physiol 307:F551-9
Saigusa, Takamitsu; Reichert, Ryan; Guare, Jennifer et al. (2012) Collecting duct cells that lack normal cilia have mislocalized vasopressin-2 receptors. Am J Physiol Renal Physiol 302:F801-8
Sas, Kelli M; Janech, Michael G; Favre, Elizabeth et al. (2011) Cilia movement regulates expression of the Raf-1 kinase inhibitor protein. Am J Physiol Renal Physiol 300:F1163-70
Bell, P Darwin; Fitzgibbon, Wayne; Sas, Kelli et al. (2011) Loss of primary cilia upregulates renal hypertrophic signaling and promotes cystogenesis. J Am Soc Nephrol 22:839-48
Sproul, Adrian; Steele, Stacy L; Thai, Tiffany L et al. (2011) N-methyl-D-aspartate receptor subunit NR3a expression and function in principal cells of the collecting duct. Am J Physiol Renal Physiol 301:F44-54
Steele, Stacy L; Wu, Yongren; Kolb, Robert J et al. (2010) Telomerase immortalization of principal cells from mouse collecting duct. Am J Physiol Renal Physiol 299:F1507-14
Siroky, Brian J; Ferguson, William B; Fuson, Amanda L et al. (2006) Loss of primary cilia results in deregulated and unabated apical calcium entry in ARPKD collecting duct cells. Am J Physiol Renal Physiol 290:F1320-8
Swystun, Veronica; Chen, Lan; Factor, Phillip et al. (2005) Apical trypsin increases ion transport and resistance by a phospholipase C-dependent rise of Ca2+. Am J Physiol Lung Cell Mol Physiol 288:L820-30

Showing the most recent 10 out of 37 publications