Effect of acute changes in glomerular filtration rate on Na+/H+ exchange in rat renal cortex.

Maddox, David A.; Fortin, Samantha M.; Tartini, A; Barnes, William D.; Gennari, F. John

doi:10.1172/jci115715

Cited by 26 publications

(16 citation statements)

References 40 publications

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“…Increasing luminal flow in the proximal tubule in rats has been found to enhance the luminal-membrane density of the Na ϩ ͞H ϩ transporter, a finding in brush-border membrane vesicles (14) and also in direct examination of pH recovery by the intact cell (13). Consistent with these observations, we found that perfusion-absorption balance is reduced significantly in NHE-3-deficient mice.…”

Section: Discussionsupporting

confidence: 87%

“…When Na ϩ reabsorption (with the control perfusate) is plotted as a function of the estimated microvillous torque, the relation is strikingly linear, with no suggestion of a transport maximum. Such linearity of reabsorption, over a broad range of delivery rates, has been a consistent finding in studies of HCO 3 Ϫ transport in the proximal tubules of rat kidneys (6,26,27). Note, however, that in the dextran perfusions, the effect of microvillous torque on reabsorption is not linear (3.6-fold torque increase in viscosity resulting in a 1.2-fold increase in reabsorption).…”

Section: Discussionsupporting

confidence: 72%

“…Preisig (13) examined recovery of cellular pH from an acute acid load in vivo (ammonium pulse) and found that increases in luminal flow rate enhanced NHE-3 activity. Maddox et al (14) subjected rats to acute changes in vascular volume to obtain hydropenic, euvolemic, and volume-expanded groups, with respective grouping according to decreased, normal, and increased glomerular-filtration rate. When brush-border membrane vesicles were prepared from each of these groups and Na ϩ -H ϩ kinetics were assessed, it was found that the maximum flux velocities stratified in parallel with the glomerular-filtration rate.…”

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confidence: 99%

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Mechanosensory function of microvilli of the kidney proximal tubule

Duan

Yan

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

104

128

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Normal variations in glomerular filtration induce proportional changes in proximal tubule Na ؉ reabsorption. This ''glomerulotubular balance'' derives from flow dependence of Na ؉ uptake across luminal cell membranes; however, the underlying physical mechanism is unknown. Our hypothesis is that flow-dependent reabsorption is an autoregulatory mechanism that is independent of neural and hormonal systems. It is signaled by the hydrodynamic torque (bending moment) on epithelial microvilli. Such signals need to be transmitted to the terminal web to modulate Na ؉ -H ؉ -exchange activity. To investigate this hypothesis, we examined Na ؉ transport and tubular diameter in response to different flow rates during the microperfusion of isolated S2 proximal tubules from mouse kidneys. The data were analyzed by using a mathematical model to estimate the microvillous torque as function of flow. In this model, increases in luminal diameter have the effect of blunting the impact of flow velocity on microvillous shear stress and, thus, microvillous torque. We found that variations in microvillous torque produce nearly identical fractional changes in Na ؉ reabsorption. Furthermore, the flow-dependent Na ؉ transport is increased by increasing luminal fluid viscosity, diminished in Na ؉ -H ؉ exchanger isoform 3 knockout mice, and abolished by nontoxic disruption of the actin cytoskeleton. These data support our hypothesis that the ''brush-border'' microvilli serve a mechanosensory function in which fluid dynamic torque is transmitted to the actin cytoskeleton and modulates Na ؉ absorption in kidney proximal tubules. glomerulotubular balance ͉ flow-dependent transport ͉ Na ϩ -H ϩ exchange

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Section: Discussionsupporting

confidence: 87%

Section: Discussionsupporting

confidence: 72%

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confidence: 99%

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Mechanosensory function of microvilli of the kidney proximal tubule

Duan

Yan

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

104

128

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“…Laminar FSS stimulates Na + and HCO 3 − absorption in the renal proximal tubule mainly by activation of the apical NHE3 and V-ATPase. This effect was repeatedly documented by groups using different experimental methods in rats (13,24). Our recent isolated single-tubule perfusion study demonstrated that the flowdependent Na + reabsorption was diminished in NHE3-null mice (3).…”

Section: Discussionmentioning

confidence: 79%

Shear stress-induced changes of membrane transporter localization and expression in mouse proximal tubule cells

Duan

Weinstein

Weinbaum

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

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Our previous studies of microperfused single proximal tubule showed that flow-dependent Na + and HCO 3 − reabsorption is due to a modulation of both NHE3 and vacuolar H + -ATPase (V-ATPase) activity. An intact actin cytoskeleton was indicated to provide a structural framework for proximal tubule cells to transmit mechanical forces and subsequently modulate cellular functions. In this study, we have used mouse proximal tubule (MPT) cells as a model to study the role of fluid shear stress (FSS) on apical NHE3 and V-ATPase and basolateral Na/K-ATPase trafficking and expression. Our hypothesis is that FSS stimulates both apical and basolateral transporter expression and trafficking, which subsequently mediates salt and volume reabsorption. We exposed MPT cells to 0.2 dynes/cm 2 FSS for 3 h and performed confocal microscopy and Western blot analysis to compare the localization and expression of both apical and basolateral transporters in control cells and cells subjected to FSS. Our findings show that FSS leads to an increment in the amount of protein expression, and a translocation of apical NHE3 and V-ATPase from the intracellular compartment to the apical plasma membrane and Na/K-ATPase to the basolateral membrane. Disrupting actin by cytochalasin D blocks the FSS-induced changes in NHE3 and Na/K-ATPase, but not V-ATPase. In contrast, FSS-induced V-ATPase redistribution and expression are largely inhibited by colchicine, an agent that blocks microtubule polymerization. Our findings suggest that the actin cytoskeleton plays an important role in FSS-induced NHE3 and Na/K-ATPase trafficking, and an intact microtubule network is critical in FSS-induced modulation of V-ATPase in proximal tubule cells. , Cl − , and water reabsorption, as well as distal Na + absorption and K + secretion (1-5). In the kidney proximal tubule, glomerular tubular balance (GTB) allows for a rapid response to the changes of glomerular filtration rate (GFR) and provides for a nearly proportional change in Na + and HCO 3 − in the fluid filtered from the glomeruli (1). The physiological importance of this regulation is to prevent loss of solute following increases in GFR, and to preserve adequate distal delivery of sodium and fluid when GFR is reduced. This highly regulated uptake of Na + and HCO 3 − depends on the activity of a group of transport proteins that are located on the luminal and peritubular membrane of proximal tubule cells. Sodium reabsorption across the proximal tubule is driven by basolateral sodium pumps (Na/K-ATPase) and enters through apical NHE3. HCO 3 − reabsorption is regulated by apical transporters NHE3 and vacuolar H + -ATPase (V-ATPase) in tandem with the basolateral Na + /HCO 3 − cotransporter (NBC). We have previously investigated the role of FSS in modulating Na + and HCO 3 − reabsorption in mouse proximal tubule (MPT) using an in vitro microperfusion technique. Our findings indicated that both NHE3 (3, 6) and V-ATPase (3) activities were enhanced by increases in luminal flow rate. These experiments confirmed that bo...

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“…The physiological importance of this regulation is to prevent loss of solute after increases in GFR and to preserve the adequate distal delivery of sodium and fluid when GFR is reduced. This highly regulated intake of Na ϩ and HCO 3 Ϫ depends on the polarized delivery of transporter proteins, such as the Na ϩ /H ϩ antiporter (NHE3) and the H ϩ -ATPase, to the apical membrane (6,7). Our in vitro microperfusion studies have shown that luminal flow modulates both NHE3 (8) and H ϩ -ATPase (3) activities, whereas disruption of the actin cytoskeleton by treatment with cytochalasin D (cD) abolished this flow-dependent behavior (8), indicating that an intact actin cytoskeleton is essential for proximal tubule cells (PTCs) to transmit flow-induced mechanical forces and subsequently modulate transport.…”

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confidence: 99%