Analysis of the sodium recirculation theory of solute-coupled water transport in small intestine

Our previous mathematical model of solute-coupled water transport through the intestinal epithelium is extended for dealing with electrolytes rather than electroneutral solutes. A 3Na(+)-2K(+) pump in the lateral membranes provides the energy-requiring step for driving transjunctional and translateral flows of water across the epithelium with recirculation of the diffusible ions maintained by a 1Na(+)-1K(+)-2Cl(-) cotransporter in the plasma membrane facing the serosal compartment. With intracellular non-diffusible anions and compliant plasma membranes, the model describes the dependence on membrane permeabilities and pump constants of fluxes of water and electrolytes, volumes and ion concentrations of cell and lateral intercellular space (lis), and membrane potentials and conductances. Simulating physiological bioelectrical features together with cellular and paracellular fluxes of the sodium ion, computations predict that the concentration differences between lis and bathing solutions are small for all three ions. Nevertheless, the diffusion fluxes of the ions out of lis significantly exceed their mass transports. It is concluded that isotonic transport requires recirculation of all three ions. The computed sodium recirculation flux that is required for isotonic transport corresponds to that estimated in experiments on toad small intestine. This result is shown to be robust and independent of whether the apical entrance mechanism for the sodium ion is a channel, a SGLT1 transporter driving inward uphill water flux, or an electroneutral Na+-K+-2Cl(-) cotransporter.