Models of coupled salt and water transport across leaky epithelia

Weinstein, Alan M.; Stephenson, John L.

doi:10.1007/bf01870828

Cited by 57 publications

(59 citation statements)

References 37 publications

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“…The reflexion coefficient at the basal opening of the lateral intercellular space towards all solutes = 0. However, the diffusive barrier between the lateral intercellular space and submucosa is an important determinant of the capacity of the tissue to move water against a transepithelial salt concentration gradient (Weinstein & Stephenson, 1981). …”

Section: Discussionmentioning

confidence: 99%

The roles of paracellular and transcellular pathways and submucosal space in isotonic water absorption by rabbit ileum.

Naftalin¹,

Tripathi²

1986

The Journal of Physiology

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(Lp) of the mucosal boundary of the lateral intercellular space is approximately 1 x 10-8 cm S-1 cmH20-1. This Lp is too low to sustain isotonicity ofthe flow emerging from the lateral intercellular space at the observed rates. Hypertonic fluid emerging from the lateral intercellular space is diluted by transcellular water flow generated by the hypertonicity of the submucosa and back-diffusion of solute via mucosal shunt

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Section: Discussionmentioning

confidence: 99%

The roles of paracellular and transcellular pathways and submucosal space in isotonic water absorption by rabbit ileum.

Naftalin¹,

Tripathi²

1986

The Journal of Physiology

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“…JNa was calculated according to the rate of fluid absorption ([Na]*Jv), since the ratio of fluid and Na ϩ absorption is 1 in the proximal tubule (53). The JCl was calculated as JCl ϭ JNa Ϫ JHCO3 (see justification in DISCUSSION).…”

Section: Methodsmentioning

confidence: 99%

Regulation of glomerulotubular balance. II. Impact of angiotensin II on flow-dependent transport

Wan

Yan

et al. 2012

American Journal of Physiology-Renal Physiology

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Underlying glomerulotubular balance (GTB) is the impact of axial flow to regulate Na ϩ and HCO 3 Ϫ transport by modulating Na ϩ -H ϩ exchanger 3 (NHE3) and H-ATPase activity. It is not known whether the cascade of events following a change in flow relies on local angiotensin (ANG II) generation or receptor availability. Mouse tubules were microperfused in vitro at flows of 5 and 20 nl/min, and net fluid (Jv) and HCO 3 Ϫ (JHCO3) absorption and cell height were measured. Na ϩ (JNa) and Cl Ϫ (JCl) absorption and changes in microvillous torque were estimated. Raising flow increased Na ϩ and HCO 3 Ϫ reabsorption but did not change either Cl Ϫ transport or cell volume. Losartan reduced absolute Na ϩ and HCO 3 Ϫ absorption at both low and high flows but did not affect fractional flowstimulated transport. Compared with controls, in AT1a knockout (KO) mouse tubules, 53% of flow-stimulated Na ϩ absorption was abolished, but flow-stimulated HCO 3 Ϫ absorption was retained at similar levels. The remaining flow-stimulated JHCO3 was eliminated by the H-ATPase inhibitor bafilomycin. Inhibition of the AT 2 receptor by PD123319 increased both J Na and JHCO3 but did not affect flowmediated fractional changes. NHE3 expression at the protein level was reduced in AT 1a KO mice kidneys. We conclude that 1) although the AT1a receptor is necessary for flow to impact NHE3, the effect on H ϩ -ATPase is independent of AT1a; 2) the small flow-mediated changes in cell volume suggest a coordinate flow effect on both luminal and basolateral transporters; and 3) there is no evidence of flow-dependent Cl Ϫ transport, and thus no evidence for convective paracellular Cl Ϫ transport in mouse tubules.angiotensin II; kidney proximal tubule; glomerulotubular balance; AT 1a,; AT2 receptor; NHE3; H-ATPase GLOMERULOTUBULAR BALANCE (GTB) refers to the proportional variation of filtered load and fluid and electrolyte reabsorption by the proximal tubule; it derives in large part from flowdependent modulation of epithelial cell transport. We have previously studied this phenomenon by examining mouse proximal tubules in vitro, measuring volume and HCO 3 Ϫ absorption under different perfusion rates and have demonstrated that both Na/H exchanger 3 (NHE3) and H-ATPase activities are modulated by axial flow (10,12). This modulation requires an intact actin cytoskeleton (10), and, as initially proposed (18), the afferent signal is flow-dependent torque (bending moment at the apical membrane due to fluid flow) on brush border microvilli (10). These previous studies are summarized elsewhere (49). ANG II directly regulates electrolyte transport along the nephron and is a key antinatriuretic signal in the proximal tubule (24, 48). ANG II can be produced within the proximal tubule from the action of a local renin and angiotensin-converting enzyme on angiotensinogen, synthesized in the liver and filtered at the glomerulus (33). Knockout of the AT 1a receptor in the proximal tubule reduced sodium absorption and blood pressure, thus demonstrating an important role of ANG...

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“…The JNa was calculated according to the rate of fluid absorption ([Na] * Jv), since the ratio of fluid and Na ϩ absorption is 1 in the proximal tubule (40). The JCl was estimated as JCl ϭ JNa Ϫ JHCO3.…”

Section: Methodsmentioning

confidence: 99%

Regulation of glomerulotubular balance. I. Impact of dopamine on flow-dependent transport

Yan

Wan

et al. 2012

American Journal of Physiology-Renal Physiology

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.-In response to volume expansion, locally generated dopamine decreases proximal tubule reabsorption by reducing both Na/H-exchanger 3 (NHE3) and Na-K-ATPase activity. We have previously demonstrated that mouse proximal tubules in vitro respond to changes in luminal flow with proportional changes in Na ϩ and HCO 3 Ϫ reabsorption and have suggested that this observation underlies glomerulotubular balance. In the present work, we investigate the impact of dopamine on the sensitivity of reabsorptive fluxes to changes in luminal flow. Mouse proximal tubules were microperfused in vitro at low and high flow rates, and volume and HCO 3 Ϫ reabsorption (Jv and J HCO3) were measured, while Na ϩ and Cl Ϫ reabsorption (JNa and JCl) were estimated. Raising luminal flow increased J v, JNa, and JHCO3 but did not change J Cl. Luminal dopamine did not change Jv, JNa, and J HCO3 at low flow rates but completely abolished the increments of Na ϩ absorption by flow and partially inhibited the flow-stimulated HCO 3 Ϫ absorption. The remaining flow-stimulated HCO 3 Ϫ absorption was completely abolished by bafilomycin. The DA1 receptor blocker SCH23390 and the PKA inhibitor H89 blocked the effect of exogenous dopamine and produced a two to threefold increase in the sensitivity of proximal Na ϩ reabsorption to luminal flow rate. Under the variety of perfusion conditions, changes in cell volume were small and did not always parallel changes in Na ϩ transport. We conclude that 1) dopamine inhibits flow-stimulated NHE3 activity by activation of the DA1 receptor via a PKA-mediated mechanism; 2) dopamine has no effect on flow-stimulated H-ATPase activity; 3) there is no evidence of flow stimulation of Cl Ϫ reabsorption; and 4) the impact of dopamine is a coordinated modulation of both luminal and peritubular Na ϩ transporters.kidney proximal tubule; sodium chloride and bicarbonate transport; DA1 and DA2 receptor function; torque KIDNEY PROXIMAL TUBULES ARE responsible for reabsorption of ϳ60% of filtered salt and water, and this fractional reabsorption is relatively constant, despite variations in the glomerular filtration rate (GFR). We have sought to understand the mechanism underlying this glomerulotubular balance (GTB) by measuring the impact of tubule perfusion rate on Na ϩ and HCO 3 Ϫ absorption in mouse proximal tubules in vitro. We have previously demonstrated that the afferent signal modulating Na ϩ and HCO 3 Ϫ transport is the flow-dependent torque (bending moment) exerted on brush border microvilli at their base (39) and that this impacts both NHE3-mediated Na ϩ and HCO 3 Ϫ absorption and H-ATPase-mediated H ϩ secretion (17, 19). The mouse proximal tubule cell was also used to examine the cellular mechanism of the flow-induced changes on NHE3 and H-ATPase expression and localization (20). In that system, fluid shear stress induces not only apical NHE3 and H-ATPase but also basolateral side Na-K-ATPase trafficking to the membrane surface. In addition, modulation of NHE3 and Na-KATPase was dependent on an intact actin cytoskeleton, ...

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Models of coupled salt and water transport across leaky epithelia

Cited by 57 publications

References 37 publications

The roles of paracellular and transcellular pathways and submucosal space in isotonic water absorption by rabbit ileum.

The roles of paracellular and transcellular pathways and submucosal space in isotonic water absorption by rabbit ileum.

Regulation of glomerulotubular balance. II. Impact of angiotensin II on flow-dependent transport

Regulation of glomerulotubular balance. I. Impact of dopamine on flow-dependent transport

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