These investigations are directed toward increasing our knowledge of the regulation of potassium transport in the colon with particular emphasis on studies in the rat. The regulation of potassium transport across intestinal and renal epithelium is critical to maintenance of potassium homeostasis. Studies performed in this laboratory during the past five years have established that several potassium transport processes are present in the colonic epithelium of the rat and that this epithelium is an excellent model for both detailed studies of intestinal potassium transport and for expanding our knowledge of potassium transport processes in general. These studies will continue investigation of potassium transport using isolated, intact colonic epithelium. Major emphasis will be placed on establishing the mechanism of active potassium absorption in the distal colonic mucosa. Our working hypothesis is that this active transport process is mediated by a K+-H+ exchange pump which may be energized by K-ATPase. Models of enhanced potassium absorption will be developed in order to determine whether there is more than one active potassium absorptive process present in the rodent colon. Active potassium secretion will be studied in three different situations -- basal transport in the proximal colon and cyclic AMP and aldosterone-stimulated secretion. These experiments will test our proposal that cyclic AMP stimulates active potassium secretion by inducing apical K conductance channels. We plan to contrast the characteristics of these three models of active potassium secretion. Studies will be extended to man to determine whether a similar active potassium absorptive process is also present in human colonic mucosa.
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