Water permeability and pathways in the proximal tubule

1983 ◽  
Vol 245 (3) ◽  
pp. F279-F294 ◽  
Author(s):  
C. A. Berry

The route of water transport in the proximal tubule could be either transjunctional or transcellular. A transjunctional route is supported by data showing high osmotic-to-diffusive water permeability ratios, the possible correlation of junctional leakiness to ions and nonelectrolytes with water permeability, and solvent drag of nonelectrolytes and ions. These data, however, are not convincing. A transcellular route of water transport is supported by data showing that the osmotic water permeability (Pf) for apical and/or basolateral cell membranes is sufficiently high to account for the transepithelial Pf, making a tentative conclusion for a transcellular route of water transport possible. In addition, measurements of Pf have yielded insights into the mechanism of solute-solvent coupling. Pf has been reported to be mostly between 0.1 and 0.3 cm/s. In the rabbit proximal straight and the Necturus proximal convoluted tubule, in which water transport rates are low, this range of Pf will account for volume absorption with only small osmotic gradients (less than 6 mosmol). Higher osmotic gradients are required in the rat and possibly the rabbit proximal convoluted tubule, where water transport rates are higher. Solute-solvent coupling in all species is probably due to both luminal hypotonicity and lateral intercellular space hypertonicity. These two processes are directly linked. Mass balance requires that generation of luminal hypotonicity also generates a hypertonic absorbate and, thus, some degree of lateral intercellular space hypertonicity. It is likely that, in the rabbit at least, effective osmotic pressure gradients due to differences in solute reflection coefficients play little role in solute-solvent coupling.

1996 ◽  
Vol 271 (4) ◽  
pp. F871-F876 ◽  
Author(s):  
R. Quigley ◽  
M. Baum

The mammalian proximal tubule reabsorbs the bulk of the glomerular filtrate in a nearly isosmotic fashion due to the high osmotic water permeability (Pf) of this segment. Although the characteristics of proximal tubule water transport have been studied in the adult proximal tubule, little is known about the neonatal segment. The present study directly measured the Pf and diffusional water permeability (PDW) of neonatal (10 +/- 2 day old) and adult rabbit juxtamedullary proximal convoluted tubules (PCT) using in vitro microperfusion. The Pf of neonatal juxtamedullary PCT was greater than the Pf of adult juxtamedullary PCT. In contrast, the PDW was not different between the two groups. The Pf and PDW values of both neonatal and adult tubules were inhibited to the same degree by p-chloromercuribenzene sulfonate and had identical activation energies. The transepithelial reflection coefficients of NaCl and NaHCO3 were also found to be similar in both the neonatal and adult proximal tubules. Thus neonatal and adult juxtamedullary PCT have many characteristics of water transport that are identical; however, neonatal Pf is three to five times that of the adult value. This difference in Pf with identical PDW values may give an insight into the transepithelial pathway for water movement in the neonatal tubule.


1987 ◽  
Vol 253 (3) ◽  
pp. F563-F575
Author(s):  
J. C. Williams ◽  
J. A. Schafer

A computer model of the proximal tubule of the rabbit is described in which the tubule is treated as a single cylindrical barrier to the flow of solute and water between lumen and bath, and volume absorption is assumed to be driven exclusively by hydrostatic and osmotic pressure differences across this barrier. The model mimics the function of the tubule in two in vitro preparations: in simulations of the isolated tubule perfused under oil, the model correctly describes the solute concentration gradients that exist between the perfusate and absorbate and predicts differences in solute concentrations among absorbate droplets on the same tubule if luminal concentration becomes limiting. This prediction was tested experimentally with glucose and found to be correct. In simulations of the tubule perfused in an aqueous bath, the role of transmural hydrostatic pressure was explored; it is predicted that, at normal rates of in vitro perfusion (approximately 10 nl/min), increases in pressure have very little effect on volume absorption but can greatly alter the osmotic differences present across the wall of the tubule, especially with high values of osmotic water permeability. At high rates of perfusion, the ability of the tubule to produce a lumen hypotonic to the bath is reduced, but the direct effects of pressure on volume absorption become more apparent, resulting in relatively little effect of perfusion rate on volume absorption if the osmotic water permeability is sufficiently high. A similar relationship was seen experimentally. In all, this simple model provides a good prediction of function in isolated perfused tubules without any assumptions of hypertonic compartments within the epithelium.


1984 ◽  
Vol 247 (5) ◽  
pp. F822-F826 ◽  
Author(s):  
F. Y. Liu ◽  
M. G. Cogan ◽  
F. C. Rector

To assess whether proximal luminal fluid becomes hypotonic with respect to plasma, free-flow micropuncture measurements were made sequentially from the end-proximal tubule to Bowman's space in 10 tubules of hydropenic Munich-Wistar rats. Osmolality in Bowman's space was 2.8 +/- 0.3 mosmol less than in plasma. Tubular fluid osmolality fell along the tubule and by the end-proximal tubule was 7.5 +/- 0.7 mosmol/kg less than in plasma or 4.7 mosmol/kg less than in Bowman's space. Since luminal fluid became hypotonic, the reabsorbate was hypertonic. The transepithelial osmotic water permeability (Pf) was calculated using simultaneously measured water reabsorption rates. The osmotic gradient responsible for water reabsorption was assumed to be either lumen-to-reabsorbate or lumen-to-peritubular plasma, with a reflection coefficient for sodium chloride of 0.7-1.0. The Pf was then estimated to be between 0.2 and 2.0 cm/s in the first millimeter of tubule and to have fallen to 0.1-0.2 cm/s by the end of the tubule. In conclusion, luminal hypotonicity develops in the rat proximal convoluted tubule and must be considered as part of the osmotic driving force for water reabsorption.


1996 ◽  
Vol 271 (2) ◽  
pp. F391-F400 ◽  
Author(s):  
D. Sun ◽  
J. A. Schafer

We studied the receptor responsible for dopamine action in isolated perfused cortical collecting ducts (CCD) from rats treated with deoxy-corticosterone. (Critical experiments were repeated in CCD from untreated rats with the same results.) At doses > or = 1 microM, dopamine inhibited arginine vasopressin (AVP)-dependent Na+ and water transport (measured by the unidirectional lumen-to-bath 22Na+ flux and the transepithelial voltage) and osmotic water permeability (Pf). The effects of dopamine were not reversed by the dopamine-1 (D1) antagonist SCH-23390, and no inhibition was produced by the D1 agonists fenoldopam or SKF-81247. When Na+ transport and Pf were stimulated with 8-(4-chlorophenylthio)adenosine 3',5'-cyclic monophosphate plus 3-isobutyl-1-methylxanthine, dopamine did not inhibit, suggesting a "D2-type" receptor. However, the D2 agonist quinpirole had no effect on the AVP-dependent transepithelial voltage (VT), and the D2 and D3 antagonists domperidone and pimozide did not reverse dopamine inhibition of VT. The only agent tested that reversed the effects of dopamine was the D4-specific antagonist clozapine. We conclude that dopamine inhibition of salt and water transport in the CCD is mediated by a D4-like receptor.


1984 ◽  
Vol 247 (5) ◽  
pp. F816-F821 ◽  
Author(s):  
F. Y. Liu ◽  
M. G. Cogan

To measure simultaneously the concentration profiles of bicarbonate, chloride and inulin along the length of the superficial proximal convoluted tubule, free-flow micropuncture measurements were made sequentially from the end-proximal tubule to Bowman's space in 10 tubules of hydropenic Munich-Wistar rats. Bicarbonate and volume reabsorption were 354 +/- 21 pmol X mm-1 X min-1 and 5.9 +/- 0.4 nl X mm-1 X min-1 in the first millimeter and fell progressively in the remaining 3.8 mm of tubule, averaging 83 +/- 4 pmol X mm-1 X min-1 and 2.3 +/- 0.5 nl X mm-1 X min-1, respectively. The values in the initial millimeter represents a high transport capacity since they exceed rates that have been observed when comparable or even higher mean luminal substrate concentrations were presented to the late proximal tubule. In contrast, chloride reabsorption was only 206 +/- 55 peq X mm-1 X min-1 in the first millimeter compared with a mean of 306 +/- 22 peq X mm-1 X min-1 in the rest of the tubule. In conclusion, there is substantial axial transport heterogeneity, with bicarbonate and water reabsorption higher but chloride reabsorption lower in the early compared with the late superficial proximal convoluted tubule.


1993 ◽  
Vol 264 (3) ◽  
pp. F397-F403 ◽  
Author(s):  
R. Mejia ◽  
M. F. Flessner ◽  
M. A. Knepper

Luminal fluid exiting the proximal convoluted tubule of a juxtamedullary nephron is alkalinized as it passes through the long-loop thin descending limb of Henle (LDL). Three potential mechanisms of alkalinization are: 1) concentration of bicarbonate by water abstraction, 2) direct bicarbonate entry, and 3) NH3 entry. We have used a mathematical model of the LDL to investigate these mechanisms. With permeabilities of HCO3-, NH3, and NH4+ measured for subsegments of the chinchilla LDL [M. F. Flessner, R. Mejia, and M. A. Knepper. Am. J. Physiol. 264 (Renal Fluid Electrolyte Physiol. 33):F388-F396, 1993], the osmotic water permeability of each segment [C.-L. Chou and M. A. Knepper. Am. J. Physiol. 263 (Renal Fluid Electrolyte Physiol. 32):F417-F426, 1992], and appropriate parameters from the literature, we have used the model to calculate hypothetical pH, HCO3- concentration, and NH3 concentration of the luminal fluid as it descends the LDL within an assumed interstitium. After eliminating each mechanism in turn by setting the appropriate permeability to zero, we recalculated the axial profiles. Our results suggest that, although all three mechanisms individually contribute to LDL alkalinization, NH3 entry likely plays the dominant role.


1984 ◽  
Vol 247 (1) ◽  
pp. F130-F139 ◽  
Author(s):  
D. W. Barfuss ◽  
J. A. Schafer

Rabbit proximal convoluted (PCT) and proximal straight tubules (PST) were perfused under oil so that droplets of absorbate could be collected. When PCT segments were perfused with an ultrafiltrate of rabbit serum or with a similar artificial solution, the osmolality of the absorbate was higher than that of the luminal perfusate by, respectively, 18.4 +/- 1.8 (SE) (P less than 0.001) or 15.8 +/- 1.9 (P less than 0.001) mosmol/kg H2O. In the PST, the absorbate osmolality was 7.7 +/- 2.6 mosmol/kg H2O (P less than 0.012) higher than an artificial perfusate solution. In the PCT the volume absorption rate was positively correlated with the osmolality difference (r = 0.653, P less than 0.002), and the slope of the linear regression line was 0.068 +/- 0.007 nl X min-1 X mm-1 X (mosmol/kg H2O)-1. Although a complete analysis based on reflection coefficients of the several solutes could not be made, this slope indicates that the maximum osmotic water permeability of the PCT in these experiments was 800-1,000 micron/s, which is significantly less than observed previously in tubules perfused in an aqueous bathing medium. The size of the osmotic gradient in the PST also implies a lower water permeability than expected. The results show, however, that a hyperosmotic absorbate can be generated by both segments when the peritubular volume is restricted. In vivo the same process would be expected to generate luminal hypotonicity.


2009 ◽  
Vol 296 (3) ◽  
pp. F649-F657 ◽  
Author(s):  
Hanne B. Moeller ◽  
Nanna MacAulay ◽  
Mark A. Knepper ◽  
Robert A. Fenton

Arginine vasopressin (AVP)-regulated phosphorylation of the water channel aquaporin-2 (AQP2) at serine 256 (S256) is essential for its accumulation in the apical plasma membrane of collecting duct principal cells. In this study, we examined the role of additional AVP-regulated phosphorylation sites in the COOH-terminal tail of AQP2 on protein function. When expressed in Xenopus laevis oocytes, prevention of AQP2 phosphorylation at S256A (S256A-AQP2) reduced osmotic water permeability threefold compared with wild-type (WT) AQP2-injected oocytes. In contrast, prevention of AQP2 single phosphorylation at S261 (S261A), S264 (S264A), and S269 (S269A), or all three sites in combination had no significant effect on water permeability. Similarly, oocytes expressing S264D-AQP2 and S269D-AQP2, mimicking AQP2 phosphorylated at these residues, had similar water permeabilities to WT-AQP2-expressing oocytes. The use of high-resolution confocal laser-scanning microscopy, as well as biochemical analysis demonstrated that all AQP2 mutants, with the exception of S256A-AQP2, had equal abundance in the oocyte plasma membrane. Correlation of osmotic water permeability relative to plasma membrane abundance demonstrated that lack of phosphorylation at S256, S261, S264, or S269 had no effect on AQP2 unit water transport. Similarly, no effect on AQP2 unit water transport was observed for the 264D and 269D forms, indicating that phosphorylation of the COOH-terminal tail of AQP2 is not involved in gating of the channel. The use of phosphospecific antibodies demonstrated that AQP2 S256 phosphorylation is not dependent on any of the other phosphorylation sites, whereas S264 and S269 phosphorylation depend on prior phosphorylation of S256. In contrast, AQP2 S261 phosphorylation is independent of the phosphorylation status of S256.


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