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 proximal tubule of the rat kidney based on kinetic descriptions of the main membrane transport systems, in order to assess the extent to which these kinetics suffice to explain certain aspects of the global transport behaviour in this segment, especially with respect to bicarbonate reabsorption. The model includes in the apical membrane, an active proton pump, Na+/H+ antiport, Na-coupled transport of organic solutes, Cl-/formate exchange with formic acid recycling, and membrane conductances to protons and K+. In the baso-lateral membrane, besides the Na+/K+ pump, the model includes Na(+)-3HCO3- and electroneutral K(+)-Cl- cotransporters, and membrane conductances for K+, H+, and, optionally, for Cl-. Appropriate passive diffusional pathways were included in both cell membranes and in the paracellular pathway. Using mass balance and electroneutrality constraints, these transport systems were built into an epithelial model which was then integrated (by finite difference approximation) into a model of a longitudinal tubule. Simulated cellular solute concentrations and luminal concentration profiles were in good agreement with reported experimental observations. We show that, given the reported transport kinetics for the Na+/H+ antiporter, a hitherto unexplained observation concerning load-dependent bicarbonate reabsorption can be shown mainly to result from the nonlinear longitudinal concentration profile for bicarbonate and pH. We also discuss problems of transcellular Cl- transport in the light of recent reports of basolateral Cl- conductance and observations relevant to apical Cl-/formate (or other base) exchange.
Thomas
S R
SR
INSERM U.323, Faculté de Médecine Necker, Paris, France.
Dagher
G
G
D000042:Absorption; D000818:Animals; D000838:Anions / Q000493:pharmacokinetics; D017920:Antiporters / Q000378:metabolism; D001639:Bicarbonates / Q000493:pharmacokinetics*; D001692:Biological Transport; D001834:Body Water / Q000378:metabolism; D002412:Cations / Q000493:pharmacokinetics; D002462:Cell Membrane / Q000378:metabolism; D016764:Cell Polarity; D003198:Computer Simulation; D004848:Epithelium / Q000378:metabolism; D007473:Ion Channels / Q000378:metabolism; D007687:Kidney Tubules, Proximal / Q000378:metabolism* / Q000648:ultrastructure; D008564:Membrane Potentials; D008871:Microvilli / Q000378:metabolism; D008954:Models, Biological; D009994:Osmolar Concentration; D051381:Rats
D000838:Anions; D017920:Antiporters; D001639:Bicarbonates; D002412:Cations; D007473:Ion Channels