The collecting duct of the mammalian kidney is an important nephron site where the excretion of water and electrolytes is regulated so as to meet the homeostatic needs of the animal. With regard to the transport of electrolytes, it is the collecting duct which plays a critical role in determining the final urinary concentrations of Na+, K+, and H+. Thus, factors which alter the transport of these ions by the collecting duct will ultimately effect whole body electrolyte balance. Although much is known about the transepithelial movement of these ions across the collecting duct epithelium, the cellular mechanisms of ion transport are largely unknown. This proposal will focus on defining the membrane electrical properties of the collecting duct, particularly as they pertain to the transport of Na+, K+, and H+. Since the collecting duct is an important site for the regulation of electrolyte excretion, studies will also be done to examine the mechanisms by which mineralocorticoid hormones, and different states of acid-base imbalance modulate these transport systems. Owing to axial heterogeneity of the rabbit collecting duct, studies of Na+ and K+ transport will be done in the cortical portion, while studies of H+ will be done in the outer medullary portion from the inner stripe. The techniques to be employed include the isolation and in vitro microperfusion of these nephron segments, and the use of electrophysiological techniques to assess the electrical consequences of ion transport. In this regard, the use of intracellular voltage recording and ion-sensitive microelectrodes will be emphasized. The long-range goal of these studies is to obtain an understanding of ion transport at the membrane level. Such studies are of general interest because the viability of the cell and the organism as a whole is dependent upon the specific and directed movement of ions into and out of the cell. This is of special interest in epithelial tissues where the cell must maintain its own internal environment in the face of net transcellular flows of solutes. Thus, understanding the driving forces and mechanisms of epithelial (renal) ion transport, particularly as related to whole body electrolyte homeostasis, is a problem of importance in both cell biology and clinical medicine.
