Mechanisms of transjunctional transport of NaCl and water in proximal tubules of mammalian kidneys.

Abstract

Tight junctions and the intercellular space of proximal tubules are not accessible to direct measurements of fluid composition and transport rates, but morphological and functional data permit analysis of diffusion and osmosis causing transjunctional NaCl and water transport. In the S2 segment NaCl diffuses through tight junctions along a chloride gradient, but against a sodium gradient. Calculation in terms of modified Nernst-Fick diffusion equation after eliminating electrical terms shows that transport rates (300-500 pmol min-1 mm-1 tubule length) and transepithelial voltage of +2 mV are in agreement with observations. Diffusion coefficients are Dtj=1500 microm2 s-1 in the S1 segment, and Dtj=90-100 microm2 s-1 in the S2 segment where apical intercellular NaCl concentration is 132 mM, 1 mM below complete stop (Dtj=0 and Donnan equilibrium). Tight junctions with gap distance 6 A are impermeable to mannitol (effective molecular radius 4 A); reflection coefficients are sigma=0.92 for NaHCO3 and sigma=0.28 for NaCl, because of difference in anion size. The osmotic force is provided by a difference in effective transjunctional osmolality of 10 mOsm kg-1 in the S1 segment and 30 mOsm kg-1 in the S2 segment, where differences in transjunctional concentration contribute with 21 mOsm kg-1 for NaHCO3 and -4 mOsm kg-1 for NaCl. Transjunctional difference of 30 mOsm kg-1 causes a volume flow of 2 nL min-1 mm-1 tubule length. Luminal mannitol concentration of 30 mM stops all volume flow and diffusive and convective transport of NaCl. In conclusion, transjunctional diffusion and osmosis along gradients generated by transcellular transport of other solutes account for all NaCl transport in proximal tubules.