Glucose Transport in a Model of the Rat Proximal Tubule Epithelium

Abstract A mathematical model of the rat proximal tubule epithelium has been extended to include terms for glucose-sodium cotransport, as well as the passive permeability properties of urea. Except for a metabolically driven Na + -K + exchanger at the cell basolateral membrane, all membrane transport is represented by the relations of linear nonequilibrium thermodynamics. Use of this formalism permits the explicit calculation of the intracellular depolarization immediately following the luminal application of glucose, and shows the magnitude of this potential deflection proportional to the glucose chemical-potential change. The steady-state glucose transport by this model epithelium, like experimental data, is fitted remarkably well by a three-parameter pump-leak model of transport. In view of the nonsaturability of the cotransporter of the model epithelium, the goodness of fit to the three-parameter model is surprising and underscores the uncertainty in extracting individual membrane properties from whole epithelial data. Experiments are simulated in which hypertonic glucose placed in the bath induces cell swelling and K + uptake; a hypertonic impermeant induces cell shrinkage and K + loss. Although this parallels the observations in vivo, the large K + shifts predicted by the model suggest the absence of important volume-regulatory mechanisms from the model scheme.