Chang, Fujita, 2001

Model Status

This CellML model is a description of Chang and Fujita's 2001 mathematical model of an anion exchanger in the distal tubule of the rat: it is one component of an overall model of acid/base transport in a distal tubule.

Model Structure

Acid-base transport in the rat distal tubule of the kidney has been extensively studied by a variety of different experimental methods. These experiments have shown that in the early part of the distal tubule, H+ is secreted into the tubular fluid via a Na/H exchanger embedded in the luminal membrane (see below). Closely linked with this process is the transport of HCO3 - out of the cytosolic space into the basolateral space. This probably occurs via an anion exchanger (see below). In the late distal tubule, distinct cell types called intercalated cells are present. These cells are specifically involved in acid-base transport. Type A cells secrete H+ via a luminal H-ATPase (see and below), and they extrude HCO3 - via a basolateral anion exchanger. Type B cells have anion transporters on their opposite side, and they function to secrete HCO3 - into the tubular fluid.

The features of acid-base transport described above are captured in the mathematical models of Hangil Chang and Toshiro Fujita (2001). Their models of transporters simulate the transport kinetics of the Na/H exchanger, anion exchanger and the H-ATPase. The raw CellML descriptions of the models can be downloaded in various formats as described in .

The complete original paper reference is cited below:

A numerical model of acid-base transport in rat distal tubule, Hangil Chang and Toshiro Fujita, 2001, American Journal of Physiology , 281, F222-F243. (PDF and text versions of the article are available to Journal subscribers. PubMed ID: 11457714)

State diagram of the Na-H exchanger. In this model, the Na-H exchanger has a single binding site (E) to which Na+, H+, and NH4 + bind competitively. Only the bound forms of the transporter are able to cross the membrane. (Symbols with the asterisk (*) represent conformations facing the cytosol, symbols without indicate conformations facing the extracellular environment.)
State diagram of the anion exchanger. In this model, the anion transporter (E) has a single binding site to which Cl- and HCO3 - competitively bind. Only the bound forms of the transporter are able to cross the membrane. (Symbols with the asterisk (*) represent conformations facing the cytosol, symbols without indicate conformations facing the extracellular environment.)
Conceptual diagram of the H-ATPase. The transporter consists of two components: a transmembrane channel and an intracellular catalytic unit. Between these two components there is a buffer space known as the antechamber, in which hydrogen ions (Ha) are in equilibrium with extracellular hydrogen ions (H) due to a large conductance of the transmembrane channel. Hydrogen ions are also moved between the antechamber and the cytosol via the catalytic unit. This ion transport is coupled to ATP hydrolysis/synthesis.
State diagram of the catalytic unit of the H-ATPase. The catalytic unit (E) has two binding sites for H. Symbols with the asterisk (*) indicate conformations of the catalytic unit in which the binding sites face the cytosol, and symbols without the asterisk represent conformations in which the binding sites face the antechamber. Transition between the unloaded conformations is coupled with ATP synthesis/hydrolysis.