Mathematical models are formulated that represent a leaky epithelium as a system of compartments and bounding membranes and permit the computer simulation of the experimental maneuvers commonly employed in physiological investigation. Further, this project undertakes the identification and analysis of simplified, or approximate, mathematical models which may be used in the reduction of experimental data. Comparison of the approximate analytical models with the output from the detailed computer simulation is used to assess the range of applicability of the simpler models and to isolate confounding influences.
A specific aim i s the construction of a model of mammalian proximal tubule--a model which will include the four ionic species (Na, K, C1, HCO3) and protein oncotic forces, allow for intraepithelial solute-solvent coupling, and track the changes in concentrations and pressures along the tubule length. This model will simulate experiments in isolated perfused tubules or micropuncture experiments in perfused kidneys in which the peritubular solution is fixed and relatively uniform. It will be the first attempt to model both the internal structure of this epithelium and the changes of the luminal fluid along the tubule length. The dynamics of water transport across proximal tubule (solute-solvent coupling, transport against an adverse osmotic gradient, isotonic transport) will be considered with the framework previously devised for the flat epithelial sheet. Analytic models of water flow across a flat epithelium will be extended to a tubular geometry. A second aspect of this project will be an examination of the predictions of the comprehensive epithelial models in simulations of electrophysiological experiments. In particular, the effect of """"""""electrically silent"""""""" events (ion-ion coupling, cell swelling) may alter intracellular potentials.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis, Diabetes, Digestive and Kidney Diseases (NIADDK)
Type
Research Project (R01)
Project #
5R01AM029857-05
Application #
3151973
Study Section
Physiology Study Section (PHY)
Project Start
1981-08-01
Project End
1987-07-31
Budget Start
1985-08-01
Budget End
1986-07-31
Support Year
5
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Weill Medical College of Cornell University
Department
Type
Schools of Medicine
DUNS #
201373169
City
New York
State
NY
Country
United States
Zip Code
10065
Weinstein, A M (1987) Convective paracellular solute flux. A source of ion-ion interaction in the epithelial transport equations. J Gen Physiol 89:501-18
Weinstein, A M (1986) An equation for flow in the renal proximal tubule. Bull Math Biol 48:29-57
Weinstein, A M (1986) Osmotic diuresis in a mathematical model of the rat proximal tubule. Am J Physiol 250:F874-84
Nachshen, D A; Sanchez-Armass, S; Weinstein, A M (1986) The regulation of cytosolic calcium in rat brain synaptosomes by sodium-dependent calcium efflux. J Physiol 381:17-28
Weinstein, A M (1986) A mathematical model of the rat proximal tubule. Am J Physiol 250:F860-73