The renal distal tubule plays an important role in regulating the urinary excretion of Na, Cl, K and H. Although the general features of ion transport by this segment have been described, the details of the cellular mechanisms which underlie transport of these ions by specific cell types are largely unknown. Accordingly, the objective of this proposal is to examine the cellular transport mechanisms of Na, Cl, K and H by direct study of single distal tubular cells.
Our specific aims i nclude: (1) Characterization of the mechanism of electroneutral NaCl absorption by the distal tubule. (2) Characterization of the mechanisms of ion transport by intercalated cells. To these ends we have developed two new experimental cell models. We will study the mechanisms of electroneutral NaCl absorption by the isolated and perfused salamander distal tubule with intracellular voltage and ion-sensitive microelectrode techniques. This segment is homologous to the mammalian distal convoluted tubule. We will also examine the conductive properties of intercalated cells in culture using patch clamp techniques on rabbit intercalated cells that have been isolated using a monoclonal antibody and immunodissection techniques. It is anticipated that these studies will significantly advance our understanding of the cellular mechanisms of electrolyte transport by well defined cells of the distal tubule and provide new insight into the regulation of transport by aldosterone and cAMP. Because electrolyte transport by distal tubular cells serves to regulate the volume and composition of the extracellular fluid, an understanding of the cellular mechanisms of electrolyte transport is a problem of importance in basic science and clinical medicine. Moreover, since electroneutral NaCl absorption by the distal tubule is inhibited by thiazide diuretics, one of the most widely used class of diuretics, information from this study will provide new information on the mechanism of action of these drugs.
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