The renal cortical collecting tubule (CCT) absorbs Na and secretes K by processes which are interrelated. There is considerable evidence that the stoichiometry is not fixed but that under some conditions the two flows can be dissociated. The isolated, perfused rabbit CCT is an ideal model for the study of K secretion because of the relatively large fluxes which can be measured. In addition, a large portion of K permeation is via a transcellular route which has a conductive component. The magnitude of the cellular K permeation appears to be increased by mineralocorticoid hormone and decreased by inhibitors of K conductive pathways. The proposed experiments will examine some of the basic properties of cellular and paracellular K permeation using four separate approaches: a) tracer permeation and transepithelial conductance measurements for conductive pathways, b) net Na, K, and Cl transport using electron probe analysis, c) intracellular measurements of membrane voltages and fractional resistances of the apical and basolateral membrane, and d) analysis of single ion channels using the patch clamp technique. In addition, cell culture techniques will be used to make unique preparations of the CCT cells. Some aspects of a model of K secretion will be examined. Experiments will probe for a KCl cotransport system on the basolateral membrane. Other experiments will examine the mechanism of inhibition of K permeation following inhibition of the Na-K pump. Another group of experiments will characterize the nature of the altered K transport following in vivo manipulations designed to greatly increase or greatly decrease K secretory rates. These results will add to our general understanding of how K excretion is regulated by the kidney. The information will be useful in understanding various states of electrolyte imbalance.
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