Membrane processes mediating K secretion

Weill Medical Coll Of Cornell Univ, New York NY

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Abstract

DESCRIPTION (provided by applicant): 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.