A new model for regulation of sodium transport in high resistance epithelia.

A new three barrier, four compartment model for sodium transport in high resistance urinary epithelia is presented. This model provides a unified and simplified mechanistic explanation for sodium transport and its quantitative regulation. Sodium enters the epithelial cell by passive diffusion. Active extrusion occurs across the lateral cell membrane into the lateral intercellular space (LICS). Sodium movement from the LICS into the serosal compartment is not free and unobstructed as in the models for low resistance epithelia, but rather occurs through a regulatory channel of the LICS passing through desmosomes and the basilar slit. The exact configuration of this regulatory channel controls the rate of sodium movement from the LICS into the serosal compartment. Thus, the configuration of the regulatory channel controls the afterload on the sodium pump and thus ultimately controls the rate of transepithelial sodium transport. Antidiuretic hormone could act by increasing the effective width of this regulatory channel by contraction of intracellular microtubules or microfilaments. Present theories for regulation of transepithelial sodium transport in high resistance epithelia invoke a regulatory barrier at the apical cell membrane or at the active sodium pump located in the basolateral cell membrane. The hypothetical model presented here invokes a new alternative: regulation of the active pump rate by the sodium concentration in the LICS serving as an afterload on the pump; sodium escape from the LICS into the serosal compartment thus becomes the regulatory step for transepithelial transport.