The basic goals of the proposed program is to investigate the mechanisms by which cellular electrolyte exchanges and renal transport processes maintain homeostatic control of electrolyte, water, and acid- base balance of the body. These issues will be approached from many different levels using a wide variety of techniques. The studies on cellular electrolyte exchanges of H, K and Na ions and the relation of these exchanges to transmembrane potential difference will be examined with direct time analysis, intracellular cation-sensitive microelectrodes, and isotopic fluxes. Basic problems in renal physiology concerning the mechanics and control of tubular transport of Na, K, Ca ions, PO4 and water will be investigated by micropuncture and in vitro microperfusion techniques utilizing rats, rabbits, hamsters and dogs. These studies are basically designed to examine the segmental membrane characteristics which regulate electrolyte and water transport, and how these processes may be influenced by various pharmacologically active agents. Clearance techniques will be used in dogs and rats to study physiologic, pathologic and pharmacologic factors which influence renal excretion of electrolytes and water. Patients with a variety of clinical disorders will be studied both by clearance and metabolic balance techniques, and when appropriate, the results of functional studies will be correlated with morphologic changes obtained by renal biopsy. Finally, in situation when it is possible, the clinical disorders will be simulated by experimental disease models in dogs and/or rats, thus permitting more intricate dissection of the pathophysiologic processes.