Mechanotransduction and water transport in rat proximal tubule.
Item
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Title
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Mechanotransduction and water transport in rat proximal tubule.
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Identifier
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AAI3103113
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identifier
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3103113
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Creator
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Guo, Peng.
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Contributor
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Mentors: Sheldon Weinbaum | Alan Weinstein
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Date
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2003
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Language
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English
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Publisher
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City University of New York.
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Subject
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Engineering, Biomedical
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Abstract
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Two long-standing mysteries in rat kidneys are explored in this dissertation: the afferent mechanism in glomerulotubular balance and the contribution of the paracellular pathway to the transepithelial water and solute transport. In the proximal tubule of rat kidneys, Na+ and HCO3 - reabsorption vary proportionally with changes in axial flow rate. This feature is a critical component of glomerulotubular balance, but the basic mechanism by which the tubule epithelial cells sense axial flow rate remains unexplained. We propose that the microvilli constituting the brush border in rat proximal tubule are physically suitable to sense the flow rate and translate this information into reabsorption. To examine this hypothesis quantitatively, we develop a hydrodynamic model to predict the force and torque distribution along a single microvillus and its resulting elastic bending deformation. This model predicts that the microvilli appear as a set of stiff bristles and are suitable to act as a mechanosensors of fluid flow and thus the afferent mechanosensory mechanism in glomerulotubular balance.;Water and solute traverse rat proximal tubule epithelium via both transcellular and paracellular routes. The tight junction (TJ) complex forms the major barrier in the paracellular route and its contribution to transepithelial water and solute transport has never been satisfactorily resolved. We first use a compartment model with revised parameter values to provide an estimation of the TJ water permeability and the TJ reflection coefficient for salts. A more general dual pathway model, large slit breaks formed by widely dispersed discontinuities and numerous small circular pores in the TJ strand, is then proposed for water and solute transport across the TJ strands. The dimensions of dual pathways are determined using the theoretically estimated values for the TJ water permeability and the TJ reflection coefficient for salts together with the TJ sucrose and NaCl permeability. It is predicted that the TJ water permeability is 21.2 percent of the transepithelial water permeability and that the small pores account for 91.2 percent of NaCl permeability, but only a few percent of the TJ water flux which crosses the TJ primarily through large slit breaks. The dimensions of dual pathways are consistent with the latest information on TJ ultrastructure.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
