Ion channels that mediate Na reabsorption by tight epithelia will be characterized, and the mechanisms by which these channels are regulated will be investigated. The major model tissue to be used will be the cortical collecting tubule of rat kidney. Apical membrane channels which are selective for Na ions and sensitive to the diuretic amiloride will be studied using the patch-clamp technique to identify ionic currents through individual channels. The biophysical nature of theses channels will be explored by assessing the selectivity of the channels for various cations, the conductance of the channels at different concentrations of permeant ions, the rates of spontaneous channel opening and closing, and the details of the ability of K-sparing diuretics to inhibit channels function. The regulation of the channels by various factors including hormones (aldosterone and ADH), external and internal ion concentrations (Ca, H and Na), the metabolic state of the tissue, and the activities of enzymes which methylate and phosphorylate membrane proteins will also be investigated. Finally, group-specific reagents will be employed to discover the chemical nature of important amino acids which govern the conductance and regulation of the channels. This project will increase the understanding of the importance process of NaCl reabsorption by epithelia, defects in which have been implicated in such diseases as cystic fibrosis, congestive heart failure and diarrhea.

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
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Physiology Study Section (PHY)
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Weill Medical College of Cornell University
Schools of Medicine
New York
United States
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Yang, Lei; Frindt, Gustavo; Lang, Florian et al. (2017) SGK1-dependent ENaC processing and trafficking in mice with high dietary K intake and elevated aldosterone. Am J Physiol Renal Physiol 312:F65-F76
Frindt, Gustavo; Gravotta, Diego; Palmer, Lawrence G (2016) Regulation of ENaC trafficking in rat kidney. J Gen Physiol 147:217-27
Frindt, Gustavo; Palmer, Lawrence G (2015) Acute effects of aldosterone on the epithelial Na channel in rat kidney. Am J Physiol Renal Physiol 308:F572-8
Palmer, Lawrence G; Schnermann, J├╝rgen (2015) Integrated control of Na transport along the nephron. Clin J Am Soc Nephrol 10:676-87
Patel, Ankit B; Yang, Lei; Deng, Su et al. (2014) Feedback inhibition of ENaC: acute and chronic mechanisms. Channels (Austin) 8:444-51
Yang, Lei; Palmer, Lawrence G (2014) Ion conduction and selectivity in acid-sensing ion channel 1. J Gen Physiol 144:245-55
Frindt, Gustavo; Li, Hui; Sackin, Henry et al. (2013) Inhibition of ROMK channels by low extracellular K+ and oxidative stress. Am J Physiol Renal Physiol 305:F208-15
Yang, Lei; Edvinsson, Johan; Sackin, Henry et al. (2012) Ion selectivity and current saturation in inward-rectifier K+ channels. J Gen Physiol 139:145-57
Yang, Lei; Edvinsson, Johan; Palmer, Lawrence G (2012) Interactions of external K+ and internal blockers in a weak inward-rectifier K+ channel. J Gen Physiol 140:529-40
Sackin, Henry; Nanazashvili, Mikheil; Li, Hui et al. (2012) Residues at the outer mouth of Kir1.1 determine K-dependent gating. Biophys J 102:2742-50

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