Previous studies in this laboratory have shown that chronic potassium loading induces an increase the rate of potassium secretion in the collecting duct system and in the colon to preserve net balance of potassium. The mechanism of this response, termed potassium adaptation, involves, at least in part, and increase in the number of Na-K-ATPase pump sites in basolateral cell membrane, and, in most epithelial segments, a rise in transepithelial potential difference. The increase in pump sites in potassium secretory cells in collecting duct and large intestine in dependent on an application of the area of the basolateral cell membrane. These adaptive epithelial changes which mediate accelerated potassium secretion are also induced by the action of aldosterone and glucocorticoids, and occur in chronic renal insufficiency. The proposed experiments have two primary aims. First, we plan to examine the mechanisms which subserve secretion and absorption of potassium in the collecting duct system and large intestine of the rat. Using techniques to measure ion transport, and electrophysiological properties, enzymatic analysis, and morphometric methods to study structure, we hope to delineate the cellular determinants of potassium transport. Second, since adrenal hormones have a powerful influence on the transport of potassium and sodium, we plan to analyze the action of both mineralocorticoids and glycocorticoids on each segment of the collecting duct system and large intestine. These experiments will utilize a new animal model developed in this laboratory which permits control of plasma levels of each class of adrenal hormones. In health the body stores of electrolytes are maintained within narrow limits due to transport mechanisms in epithelia lining the renal tubule and intestine which regulate the rate of excretion in a way that equals intake. The proposed studies are designed to provide new insights into the adaptive processes which control potassium excretion and, hopefully will have important implications in our understanding of epithelial adaptations as a general phenomena.

National Institute of Health (NIH)
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
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General Medicine B Study Section (GMB)
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Yale University
Schools of Medicine
New Haven
United States
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