Osmotic gradient dependence of osmotic water permeability in rabbit proximal convoluted tubule

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Abstract
To assess steady-state transepithelial osmotic water permeability (P f ), rabbit proximal convoluted tubules were perfused in vitro with the impermeant salt, sodium isethionate at 26°C. Osmotic gradients (ΔΠ) were established by varying the bath concentration of the impermeant solute, raffinose. When lumen osmolality was 300 mOsm and bath osmolality was 320, 360 and 400 mOsm, apparentP f decreased from 0.5 to 0.10 to 0.08 cm/sec, respectively. Similar data were obtained when lumen osmolality was 400 mOsm. Five possible causes of the ΔΠ dependence of apparentP f were considered experimentally and/or theoretically: (1) external unstirred layer (USL); (2) cytoplasmic USL; (3) change in surface area; (4) saturation of water transport; (5) down-regulation ofP f . ApparentP f was inhibited 83% byp-chloromercuribenzene sulfonate (pCMBS) at 20 mOsm, but not at 60 mOsm ΔΠ, suggesting presence of a serial barrier resistance to water transport. Increases in perfusate or bath solution flow rate and viscosity did not alter apparentP f , ruling out an external USL. A simple cytoplasmic USL, described by a constant USL thickness and solute diffusion coefficient, could not account for the ΔΠ dependence of apparentP f according to a mathematical model. The activation energy (E a ) for apparentP f increased from 7.0 to 12.5 kcal/mol when ΔΠ was increased from 20 to 60 mOsm, not consistent with a simple USL or a change in membrane surface area with transepithelial water flow. These findings are most consistent with a complex cytoplasmic USL, where the average solute diffusion coefficient and/or the area available for osmosis decrease with increasing ΔΠ. These results (1) indicate that trueP f (at physiologically low ΔΠ) is very high (>0.5 cm/sec) in the rabbit proximal tubule; (2) provide an explanation for the wide variation inP f values reported in the literature using different ΔΠ, and (3) suggest the presence of a flow-dependent cytoplasmic barrier to water flow.

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