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      Transepithelial Ca 2+ and Mg 2+ Transport in the Cortical Thick Ascending Limb of Henle’s Loop of the Mouse Is a Voltage-Dependent Process

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          Abstract

          The mechanisms responsible for transepithelial Ca<sup>2+</sup> and Mg<sup>2+</sup> transport in the isolated perfused cortical thick ascending limb (cTAL) of Henle’s loop of the mouse nephron were investigated by measuring transepithelial voltages (PD<sub>te</sub>) and transepithelial ion net fluxes (J<sub>Na</sub>, J<sub>c1</sub>, J<sub>ĸ</sub>, J<sub>ca</sub>, J<sub>Mg</sub>) by electron microprobe analysis. In the presence of furosemide (10<sup>-4</sup> mol·l<sup>-1</sup>, lumen) and diphenylamine-2-carboxylate (DPC, 10<sup>-4</sup> mol·l<sup>-1</sup>, bath), known inhibitors of NaCl reabsorption in the TAL, Ca<sup>2+</sup> and Mg<sup>2+</sup> reabsorption was completely inhibited. In the presence of furosemide, J<sub>Ca</sub> fell from 0.75 ± 0.07 to -0.08 ± 0.09 pmol·min<sup>-1</sup>.mm<sup>-1</sup> (n = 5) and J<sub>Mg</sub> from 0.47 ± 0.04 to -0.01 ± 0.11 pmol·min<sup>-1</sup>.mm<sup>-1</sup> (n = 5). In the presence of DPC, J<sub>Ca</sub> fell from 0.57 ± 0.08 to -0.07 ± 0.11 pmol·min<sup>-1</sup>.mm<sup>-1</sup> (n = 5), and J<sub>Mg</sub> from 0.16 ± 0.02 to-0.11 ± 0.07pmol·min<sup>-1</sup>·mm<sup>-1</sup>(n = 5). With furosemide, inhibition of Ca<sup>2+</sup> and Mg<sup>2+</sup> transport was paralleled by a 93% inhibition of NaCl reabsorption, while in the presence of DPC there was a 60% reduction of NaCl reabsorption. These effects were fully reversed after removal of the inhibitors from the lumen or bath solutions. In the absence of active NaCl transport, a lumen-to-bath directed-NaCl gradient (lumen: 150 m M NaCl + furosemide, bath: 50 m M NaCl + 200 m M mannitol) generated a negative transepithelial dilution potential of-13.8 ± 1.1 mV (n = 8) which induced a significant Ca<sup>2+</sup> and Mg<sup>2+</sup> secretion into the tubular lumen of -0.59 ± 0.06 and 0.43 ± 0.05pmol·min<sup>-1</sup>·mm<sup>-1</sup> (n = 8), respectively. Abath-to-lumen-directed NaCl gradient on the other hand (lumen: 50 m M NaCl + furosemide, bath: 150m M NaCl) generated a positive transepithelial dilution potential of +15.9 ± 0.6 mV (n = 7), inducing a significant Ca<sup>2+</sup> and Mg<sup>2+</sup> reabsorption of 0.62 ± 0.08 and 0.38 ± 0.07 pmol·min<sup>-1</sup> mm<sup>-1</sup>(n = 7), respectively. Linear regression analysis of individual Ca<sup>2+</sup> and Mg<sup>2+</sup> net flux data versus voltage indicated that J<sub>Ca</sub> and J<sub>Mg</sub> were highly correlated to PD<sub>te</sub>. In conclusion, these data indicate that transepithelial Ca<sup>2+</sup> and Mg<sup>2+</sup> reabsorption in the mouse cTAL is predominantly a passive process, driven by the lumen-positive PD<sub>te</sub>.

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          Author and article information

          Journal
          KBR
          Kidney Blood Press Res
          10.1159/issn.1420-4096
          Kidney and Blood Pressure Research
          S. Karger AG
          1420-4096
          1423-0143
          1993
          1993
          11 November 2008
          : 16
          : 4
          : 157-166
          Affiliations
          Service de Biologie Cellulaire, Département de Biologie Cellulaire et Moléculaire, CE Saclay, Gif-sur-Yvette, France
          Article
          173762 Renal Physiol Biochem 1993;16:157–166
          10.1159/000173762
          a2d8aa41-2374-4cb1-a580-d4f592e6e9bc
          © 1993 S. Karger AG, Basel

          Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

          History
          : 22 January 1993
          Page count
          Pages: 10
          Categories
          Original Paper

          Cardiovascular Medicine,Nephrology
          Ca2+ transport,Diphenylamine-2-carboxylate,Electron microprobe,Cortical thick ascending limb,Furosemide,Mg2+ transport,Passive permeability

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