A dual-pathway ultrastructural model for the tight junction of rat proximal tubule epithelium

2003 ◽  
Vol 285 (2) ◽  
pp. F241-F257 ◽  
Author(s):  
Peng Guo ◽  
Alan M. Weinstein ◽  
Sheldon Weinbaum

A dual-pathway model is proposed for transport across the tight junction (TJ) in rat proximal tubule: large slit breaks formed by infrequent discontinuities in the TJ complex and numerous small circular pores, with spacing similar to that of claudin-2. This dual-pathway model is developed in the context of a proximal tubule model (Weinstein AM. Am J Physiol Renal Fluid Electrolyte Physiol 247: F848–F862, 1984) to provide an ultrastructural view of solute and water fluxes. Tubule model paramters (TJ reflection coefficient and water permeability), plus the measured epithelial NaCl and sucrose permeabilities, provide constraints for the dual-pathway model, which yields the small-pore radius and spacing and large slit height and area. For a small-pore spacing of 20.2 nm, comparable to the distance between adjacent particle pairs in apposing TJ strands, the small-pore radius is 0.668 nm and the large slit breaks have a height of 19.6 nm, occupying 0.04% of the total TJ length. This pore/slit geometry also satisfies the measured permeability for mannitol. The numerous small circular pores account for 91.25% of TJ NaCl permeability but only 5.0% of TJ water permeability. The infrequent large slit breaks in the TJ account for 95.0% of TJ water permeability but only 8.7% of TJ NaCl permeability. Sucrose and mannitol (4.6- and 3.6-Å radius) can pass through both the large slit breaks and the small pores. For sucrose, 78.3% of the flux is via the slits and 21.7% via the pores; for mannitol, the flux is split nearly evenly between the two pathways, 50.8 and 49.2%. In this ultrastructural model, the TJ water permeability is 21.2% of the entire transepithelial water permeability and thus an order of magnitude greater than that predicted by the single-pore/slit theory (Preisig PA and Berry CA. Am J Physiol Renal Fluid Electrolyte Physiol 249: F124–F131, 1985).

1990 ◽  
Vol 258 (3) ◽  
pp. F612-F626 ◽  
Author(s):  
A. M. Weinstein

A nonelectrolyte model of proximal tubule epithelium has been extended by the inclusion of a compliant tight junction. Here "compliance" signifies that both the junctional salt and water permeability increase and the salt reflection coefficient decreases in response to small pressure differences from lateral interspace to tubule lumen. In previous models of rat proximal tubule, there has been virtually no sensitivity of isotonic salt transport to changes in peritubular oncotic force. With the inclusion of junctional compliance, decreases in peritubular protein can open the junction and produce a secretory salt flux. Thus the model can represent the "backflux hypothesis," as it was originally put forth (J. E. Lewy and E. E. Windhager, Am. J. Physiol. 214: 943-954, 1968). Additional calculations, simulating a tight junction with negligible water permeability, reveal that the quantitative impact of peritubular protein can be realized whether or not there is substantial junctional water flux. The epithelial model of proximal tubule has also been incorporated into a model of the proximal nephron, complete with glomerulus, peritubular capillary, and interstitium. The interstitial compartment is well mixed and interstitial pressure and osmolality are determined iteratively to achieve balance between tubule reabsorption and capillary uptake. For this model, two domains of operation are identified. When interstitial pressures are low, junctions are closed, and filtration fraction has no effect on proximal reabsorption. When interstitial pressures are relatively elevated, epithelial junctions are open, and proximal salt reabsorption changes in proportion to changes in filtration fraction. In neither domain, however, does the model tubule augment salt flux with isolated increases in luminal flow rate (at constant filtration fraction). The absence of a separate effect of tubule fluid flow on salt transport precludes perfect glomerulotubular balance.


1989 ◽  
Vol 257 (4) ◽  
pp. F658-F668 ◽  
Author(s):  
R. Green ◽  
G. Giebisch

Simultaneous microperfusion of proximal tubules and peritubular capillaries in kidneys of rats anesthetized with Inactin was used to measure reflection coefficients. All perfusates contained cyanide to inhibit active transport; the tubular perfusate was isotonic and the peritubular capillaries were perfused with solutions made hypertonic with NaCl, NaHCO3, L-glucose, or sodium ferrocyanide. Measurements of recollected fluid enabled a precise mean gradient and ionic fluxes to be calculated; net water flux was measured with inulin. Imposed gradients always partly dissipated. Reflection coefficients were 0.59 +/- 0.01 for NaCl, 0.87 +/- 0.04 for NaHCO3-, and 0.96 +/- 0.07 for ferrocyanide, assuming that L-glucose was 1. Water permeability of the proximal tubule was 1,030 microns/s. Ionic permeability of Cl- (21.6 +/- 1.3 X 10(-5) cm/s) was greater than that for Na+ (13.3 +/- 2.7 X 10(-5) cm/s); permeability for L-glucose was 5.4 +/- 1.3 X 10(-5), and for ferrocyanide ions 2.7 +/- 0.9 X 10(-5) cm/s. It is concluded that in rat proximal tubule both NaCl and NaHCO3 have reflection coefficients less than 1.0 and solute asymmetry across the epithelium is a significant driving force for fluid reabsorption. Furthermore the data suggest that there is a significant contribution of solvent drag to solute movement.


Author(s):  
Haixiao Chen ◽  
Ho Kwong Kwan ◽  
Jie Xin

AbstractThis research examines the mixed work-to-family spillover effects of unethical pro-organizational behavior. Drawing on conservation of resources theory and the work–home resources model, we develop a dual-pathway model to explain such effects. Based on a three-wave field study involving 214 respondents in China, we find engagement in unethical pro-organizational behavior to be positively associated with employees’ organization-based self-esteem and stress at work, which in turn, leads to work-to-family positive spillover and work-to-family conflict, respectively. We also find that performing tensions moderate the mixed effects of unethical pro-organizational behavior on organization-based self-esteem and work stress and the indirect effects of unethical pro-organizational behavior on work-to-family positive spillover and work-to-family conflict. Our findings have theoretical implications for business ethics scholars and practical implications for managers.


1997 ◽  
Vol 19 (2) ◽  
pp. 161-170 ◽  
Author(s):  
Glenn Affleck ◽  
Susan Urrows ◽  
Howard Tennen ◽  
Pamela Higgins ◽  
Dawn Pav ◽  
...  

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