The delineation of various structural-functional relationships in the mammalian nephron represents the major research goal of this proposal. Most segments of the protocol involve a combined morphological-physiological investigative approach and employ a variety of laboratory techniques including transmission electron microscopy, scanning electron microscopy, light microscopy, micropuncture, microperfusion of isolated tubule segments, freeze-fracture electron microscopy, and radioautography. Specific projects include the delineation of the precise site of organic base secretion in the rabbit proximal tubule, freeze-fracture examination of the plasma membranes and junctional complexes of the proximal tubule under normal conditions and during physiological maneuvers designed to enhance backleak through the paracellular shunt pathway, examination of the mechanism of phagocytosis in the proximal tubule, freeze-fracture examination of the ascending thick limb, comparison of the ultrastructural configuration of the ascending thick limb of juxtamedullary and superficial nephrons, examination of the morphological response of the renal glomerulus to major alterations in renal perfusion pressure which are known to alter the ultrafiltration characteristics of that segment of the nephron, continued detailed morphological analysis of the nondiseased mammalian kidney using the primary mode of scanning electron microscopy, and evaluation of the macula densa as a receptor in the mechanism controlling renin release, and as a receptor in the mechanism of feedback control of glomerular filtration at the single nephron level.
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