Mechanisms of intercellular hypertonicity and isotonic fluid absorption in proximal tubules of mammalian kidneys.

The main purpose of this theoretical analysis (second of two articles) is to examine whether transjunctional diffusion of NaCl causes intercellular hypertonicity, which permits transcellular water transport across solute-impermeable lateral cell membranes until osmotic equilibration. In the S2 segment with tubular NaCl concentration 140 mM, the calculated apical intercellular NaCl concentration is c0 approximately 132 mM, which exceeds peritubular NaCl concentration by 12 mM or 22 mOsm kg-1. Variations in volume flow, junctional reflection coefficient (sigmaNaCl = 0.25-0.50), gap distance (g = 6-8 A), junctional depth (d = 18-100 A), intercellular diffusion coefficient (DLIS=500-1500 microm2 s-1) and hypothetical active NaCl transport alter c0 only by a fraction of 1 mM. However, dilution and back-leakage of NaHCO3 lower apical intercellular hyperosmolality to approximately 18 mOsm kg-1. Water transport through solute-impermeable lateral cell membranes continues until intercellular and cellular osmolalities are equal. Transcellular and transjunctional volume flow are of similar magnitude (2 nL min-1 mm-1 tubule length) in the S2 segment. Thus, diffusion ensures isotonic absorption of NaCl. Two-thirds of NaHCO3 and other actively transported sodium salts are extruded into the last third of the exponentially widening intercellular space where the exposure time is only 0.9 s. Osmotic equilibration is dependent on aquaporins in the cell membranes. If permeability to water is low, transcellular water transport stops; tubular fluid becomes hypotonic; NaCl diffusion diminishes, but transjunctional water transport remains unaltered as long as transcellular transport of NaHCO3 and other solutes provides the osmotic force.