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      Separation of two Cl Currents in Cultured Human and Murine Mesangial Cells: Biophysical and Pharmacological Characteristics of I Cl.vol and I Cl.Ca

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          Abstract

          Mesangial cells, a combined smooth muscle- and fibroblast-like phenotype, are important regulators of renal function. These cells exist in a region of variable osmolarity and may require Cl<sup>–</sup> channels for volume regulation. Additionally, Ca<sup>2+</sup>-activated Cl<sup>–</sup> channels in these cells may participate in Ca<sup>2+</sup>-dependent contractile responses to vasoactive agonists. Relatively little, however, is known about mesangial cell Cl<sup>–</sup> currents (I<sub>Cl</sub>); including the biophysical description and pharmacological characterization. We used whole-cell patch clamp to study I<sub>Cl</sub> in cultured human and SV40-transformed murine mesangial cells. I<sub>Cl</sub> was measured in cells dialyzed and bathed with symmetrical N-methyl- D-glucamine chloride solutions to minimize cation currents. Dialysis with buffers to control intracellular Ca<sup>2+</sup> ([Ca<sup>2+</sup>]<sub>i</sub>), extracellular solutions of varied osmolarity, and manipulation of the transmembrane Cl<sup>–</sup> gradient were used to separate two currents: I<sub>Cl.vol</sub> (volume-sensitive), and I<sub>Cl.Ca</sub> (Ca<sup>2+</sup>-activated). In symmetrical Cl<sup>–</sup> with low [Ca<sup>2+</sup>]<sub>i</sub>, I<sub>Cl.vol</sub> was outwardly rectifying and modulated by osmolarity. I<sub>Cl.vol</sub> demonstrated slight time- and voltage-dependent inactivation. In symmetrical Cl<sup>–</sup> with elevated [Ca<sup>2+</sup>]<sub>i</sub> and hypertonic bath, I<sub>Cl.Ca</sub> was linear, but in asymmetrical Cl<sup>–</sup> (low [Cl<sup>–</sup>]<sub>i</sub>) was outwardly rectifying and demonstrated time- and voltage-dependent activation. Permeability sequences for both I<sub>Cl.vol</sub> and I<sub>Cl.Ca</sub> were I<sup>–</sup> > Br<sup>–</sup> > Cl<sup>–</sup> > F<sup>–</sup>; however, there were differences in the relative magnitudes. Tamoxifen inhibited I<sub>Cl.vol</sub> more potently than I<sub>Cl.Ca</sub>, whereas niflumic acid inhibited I<sub>Cl.Ca</sub> more potently than I<sub>Cl.vol</sub>. We have separated and characterized two types of I<sub>Cl</sub> in cultured human and murine mesangial cells. I<sub>Cl.Ca</sub> and I<sub>Cl.vol</sub> have different biophysical and pharmacological characteristics. These observations on I<sub>Cl.Ca</sub> and I<sub>Cl.vol</sub> may provide insight into mesangial cell reactivity and volume regulation.

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          Author and article information

          Journal
          JVR
          J Vasc Res
          10.1159/issn.1018-1172
          Journal of Vascular Research
          S. Karger AG
          1018-1172
          1423-0135
          2002
          October 2002
          18 September 2002
          : 39
          : 5
          : 426-436
          Affiliations
          Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, Nev., USA
          Article
          64516 J Vasc Res 2002;39:426–436
          10.1159/000064516
          12297705
          © 2002 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.

          Page count
          Figures: 6, References: 40, Pages: 11
          Categories
          Research Paper

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