HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 290/2/F289    most recent 00255.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (10) Citing Articles via Google Scholar Google Scholar Articles by Du, Z. Articles by Wang, T. Search for Related Content PubMed PubMed Citation Articles by Du, Z. Articles by Wang, T.

Axial flow modulates proximal tubule NHE3 and H-ATPase activities by changing microvillus bending moments

¹Department of Cellular and Molecular Physiology, Yale University, New Haven, Connecticut; ²Department of Biomedical Engineering, The City College of New York, City University of New York; and ³Department of Physiology and Biophysics, Weill Medical College of Cornell University, New York, New York

Submitted 20 June 2005 ; accepted in final form 24 August 2005

We have previously demonstrated that mouse proximal tubules in vitro respond to changes in luminal flow with proportional changes in Na⁺ absorption (Du Z, Duan Y, Yan Q, Weinstein AM, Weinbaum S, and Wang T. Proc Natl Acad Sci USA 101: 13068–13073, 2004). It was hypothesized that brush-border microvilli function as a sensor to detect and amplify luminal hydrodynamic forces and transmit them to the actin cytoskeleton. In the present study we examine whether 1) flow-dependent HCO₃^– transport is proportional to flow-dependent variations in microvillous torque (bending moment); 2) both luminal membrane Na⁺/H⁺ exchange (NHE3) and H⁺-ATPase activity are modulated by axial flow; and 3) paracellular permeabilities contribute to the flux perturbations. HCO₃^– absorption is examined by microperfusion of mouse S2 proximal tubules in vitro, with varying perfusion rates, and in the presence of the Na/H-exchange inhibitor EIPA, the H⁺-ATPase inhibitor bafilomycin, and the actin cytoskeleton inhibitor cytochalasin D. Paracellular permeability changes are assessed with measurements of epithelial HCO₃^– permeability and transepithelial potential difference (PD). It is found that 1) an increase in perfusion rate enhances HCO₃^– absorption and microvillous torque, and the fractional changes of each are nearly identical; 2) inhibition of NHE3 by EIPA, or H⁺-ATPase by bafilomycin, produced only partial inhibition of flow-stimulated bicarbonate transport; 3) disruption of the actin cytoskeleton by cytochalasin D blocked the increment of HCO₃^– absorption by high flow; and 4) HCO₃^– permeability and transepithelial PD are not modulated by flow. We conclude that flow-dependent modulation of proximal tubule HCO₃^– reabsorption is due to changes in both NHE3 and H⁺-ATPase activity within the luminal cell membrane and this requires an intact actin cytoskeleton. Paracellular permeability changes do not contribute to this flow dependence. Perfusion-absorption balance in the proximal tubule is a direct effect of flow-induced torque on brush-border microvilli to regulate luminal cell membrane transporter activity.

kidney proximal tubule; glomerulotubular balance; flow-dependent transport; sodium-hydrogen exchange

This article has been cited by other articles:

				Y. Duan, N. Gotoh, Q. Yan, Z. Du, A. M. Weinstein, T. Wang, and S. Weinbaum Shear-induced reorganization of renal proximal tubule cell actin cytoskeleton and apical junctional complexes PNAS, August 12, 2008; 105(32): 11418 - 11423. [Abstract] [Full Text] [PDF]

				M. R. Quinlan, N. G. Docherty, R. W. G. Watson, and J. M. Fitzpatrick Exploring mechanisms involved in renal tubular sensing of mechanical stretch following ureteric obstruction Am J Physiol Renal Physiol, July 1, 2008; 295(1): F1 - F11. [Abstract] [Full Text] [PDF]

				C. A. Wagner, D. Loffing-Cueni, Q. Yan, N. Schulz, P. Fakitsas, M. Carrel, T. Wang, F. Verrey, J. P. Geibel, G. Giebisch, et al. Mouse model of type II Bartter's syndrome. II. Altered expression of renal sodium- and water-transporting proteins Am J Physiol Renal Physiol, June 1, 2008; 294(6): F1373 - F1380. [Abstract] [Full Text] [PDF]

				M. Donowitz and X. Li Regulatory Binding Partners and Complexes of NHE3 Physiol Rev, July 1, 2007; 87(3): 825 - 872. [Abstract] [Full Text] [PDF]

				A. M. Weinstein, S. Weinbaum, Y. Duan, Z. Du, Q. Yan, and T. Wang Flow-dependent transport in a mathematical model of rat proximal tubule Am J Physiol Renal Physiol, April 1, 2007; 292(4): F1164 - F1181. [Abstract] [Full Text] [PDF]

				C. Xu, S. Rossetti, L. Jiang, P. C. Harris, U. Brown-Glaberman, A. Wandinger-Ness, R. Bacallao, and S. L. Alper Human ADPKD primary cyst epithelial cells with a novel, single codon deletion in the PKD1 gene exhibit defective ciliary polycystin localization and loss of flow-induced Ca2+ signaling Am J Physiol Renal Physiol, March 1, 2007; 292(3): F930 - F945. [Abstract] [Full Text] [PDF]