A KINETIC-MODEL OF RAT PROXIMAL TUBULE TRANSPORT - LOAD-DEPENDENT BICARBONATE REABSORPTION ALONG THE TUBULE

A model is presented of solute and water reabsorption along the proxim al tubule of the rat kidney based on kinetic descriptions of the main membrane transport systems, in order to assess the extent to which the se kinetics suffice to explain certain aspects of the global transport behaviour in this segment, especially with respect to bicarbonate rea bsorption. The model includes in the apical membrane, an active proton pump, Na+/H+ antiport, Na-coupled transport of organic solutes, Cl-/f ormate exchange with formic acid recycling, and membrane conductances to protons and K+. In the baso-lateral membrane, besides the Na/K+ pum p, the model includes Na+-3HCO3- and electroneutral K+-Cl- cotransport ers, and membrane conductances for K+, H+, and, optionally, for Cl-. A ppropriate passive diffusional pathways were included in both cell mem branes and in the paracellular pathway. Using mass balance and electon eutrality constraints, these transport systems were built into an epit helial model which was then integrated (by finite difference approxima tion) into a model of a longitudinal tubule. Simulated cellular solute concentrations and luminal concentration profiles were in good agreem ent with reported experimental observations. We show that, given the r eported transport kinetics for the Na+/H+ antiporter, a hitherto unexp lained observation concerning load-dependent bicarbonate reabsorption can be shown mainly to result from the nonlinear longitudinal concentr ation profile for bicarbonate and pH. We also discuss problems of tran scellular Cl- transport in the light of recent reports of basolateral Cl- conductance and observations relevant to apical Cl-/formate (or ot her base) exchange.