The kidneys maintain constant levels of K+ in the plasma and extracellular fluids by matching urinary excretion of the ions to dietary intake. This process involves a complex signaling system through which the renal tubular cells interact with the plasma K+ concentration and perhaps also with the gut and endocrine organs. However the nature of this system is not well understood. We will examine how this process works by assessing the function of K+ channels in the apical membrane of the rat connecting tubule and collecting duct. These channels are thought to be the key pathway through which K+ is secreted into the urine. We will measure the overall activity of the channels using electrophysiological techniques, the total abundance of channels using immunoblotting, and the amount of protein in the apical membrane using a biotinylation approach for labeling proteins at the cell surface. We will correlate these parameters with parallel measurements of Na channel activity and NaCl-cotransporter expression. We will test the hypothesis that the serine/threonine kinase SGK1 plays an important role in the modulation of these processes and of renal K excretion. We will also assess the ability of insulin to acutely influence K+ transport in distal nephron segments. Finally, we will examine the interactions between these channels and intracellular Mg2+, changes of which may be important in pathological conditions involving Mg depletion or wasting.

Public Health Relevance

Proper function of the kidneys is essential for maintaining the optimal concentration of potassium ions in the body fluids. Concentrations that are either too high or two low lead to cardiac arrhythmias or in the extreme case to cardiac arrest. We will study how the kidneys keep the levels of this ion constant by measuring the amount and the function of proteins at the surface of kidney cells that allow potassium to be transported into the urine, where it is eventually excreted from the body. Understanding how this process works and how it changes in response to different amounts of potassium in the diet will help in the management and treatment of patients with hypokalemia and hyperkalemia.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK027847-30
Application #
8284412
Study Section
Cellular and Molecular Biology of the Kidney Study Section (CMBK)
Program Officer
Ketchum, Christian J
Project Start
1981-03-01
Project End
2014-06-30
Budget Start
2012-07-01
Budget End
2013-06-30
Support Year
30
Fiscal Year
2012
Total Cost
$347,168
Indirect Cost
$141,743
Name
Weill Medical College of Cornell University
Department
Physiology
Type
Schools of Medicine
DUNS #
060217502
City
New York
State
NY
Country
United States
Zip Code
10065
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
Frindt, Gustavo; Palmer, Lawrence G (2012) Effects of insulin on Na and K transporters in the rat CCD. Am J Physiol Renal Physiol 302:F1227-33
Frindt, Gustavo; Houde, Veronique; Palmer, Lawrence G (2011) Conservation of Na+ vs. K+ by the rat cortical collecting duct. Am J Physiol Renal Physiol 301:F14-20
Wade, James B; Fang, Liang; Coleman, Richard A et al. (2011) Differential regulation of ROMK (Kir1.1) in distal nephron segments by dietary potassium. Am J Physiol Renal Physiol 300:F1385-93
Edvinsson, Johan M; Shah, Anish J; Palmer, Lawrence G (2011) Kir4.1 K+ channels are regulated by external cations. Channels (Austin) 5:269-79
Edvinsson, Johan M; Shah, Anish J; Palmer, Lawrence G (2011) Potassium-dependent activation of Kir4.2 Kýýý channels. J Physiol 589:5949-63
Frindt, Gustavo; Palmer, Lawrence G (2010) Effects of dietary K on cell-surface expression of renal ion channels and transporters. Am J Physiol Renal Physiol 299:F890-7
Yang, Lei; Frindt, Gustavo; Palmer, Lawrence G (2010) Magnesium modulates ROMK channel-mediated potassium secretion. J Am Soc Nephrol 21:2109-16

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