+1 Recommend
1 collections
      • Record: found
      • Abstract: found
      • Article: found

      Influence of Calcium on Regulatory Volume Decrease: Role of Potassium Channels

      Read this article at

          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.


          In most cell types, hyposmotic swelling consistently elicits an increase in the concentration of cytosolic Ca<sup>2+</sup> – [Ca<sup>2+</sup>]<sub>i</sub> – with contributions of extracellular and intracellular sources. The mechanisms of Ca<sup>2+</sup> entry and release from endogenous sources are not fully clarified and may be cell specific. The ubiquity of the swelling-evoked [Ca<sup>2+</sup>]<sub>i</sub> rise makes Ca<sup>2+</sup> a likely candidate for a role as osmotransducing signal. However, the regulatory volume decrease (RVD) which follows swelling and the osmolyte fluxes involved in this process are not always Ca<sup>2+</sup> dependent. It was found that, with a few exceptions, in most cell types the osmosensitive Cl<sup>–</sup> efflux pathway and the swelling-activated organic osmolyte fluxes are Ca<sup>2+</sup> independent. In contrast, Ca<sup>2+</sup>-dependent or Ca<sup>2+</sup>-independent K<sup>+</sup> fluxes activated by swelling are detected, depending on the cell type. The close correlation found in this review between the Ca<sup>2+</sup> dependence of RVD and that of the K<sup>+</sup> channels activated by swelling led to the conclusion that it is the type of osmosensitive K<sup>+</sup> pathway which largely confers the Ca<sup>2+</sup> dependence to RVD. Interestingly, this coincidence of Ca<sup>2+</sup>-dependent K<sup>+</sup> efflux and RVD is found predominantly in epithelial cells, whereas in nonepithelial cells both processes are largely Ca<sup>2+</sup> independent. In these cells, the [Ca<sup>2+</sup>]<sub>i</sub> rise elicited by swelling may be an epiphenomenon.

          Related collections

          Most cited references 21

          • Record: found
          • Abstract: found
          • Article: not found

          Mediation of cell volume regulation by Ca2+ influx through stretch-activated channels.

          Animal cells initially swell in hypotonic media by osmotic water equilibration, but their volume is subsequently regulated by a net loss of KCl and amino acids with concomitant loss of cell water. Mechanisms for regulating cell volume are important in allowing cells to adapt to variations in external tonicity and metabolic load. In red cells the KCl loss is mediated by electroneutral ion transport mechanisms. In contrast, conductive K+ and Cl- transport pathways are activated during regulatory volume decrease in several cell types including epithelia. The activation seems to be mediated by internal Ca2+, but the detailed mechanism is not known. In a leaky epithelium, the choroid plexus epithelium, we have found a cation-selective, Ca2+-permeable channel which opens with membrane stretch. The epithelium also contains a high density of the large (approximately 200 pS) type of Ca2+- voltage-activated K+ channel. Both channels are normally closed. I propose that in hypotonic media, the stretching of the cell membrane produced by the initial swelling causes influx of Ca2+ through the stretch-activated channels, which activates the neighbouring large K+ channels to produce increased K+ outflux with associated loss of cell water.
            • Record: found
            • Abstract: found
            • Article: not found

            The Tyrosine Kinase p56lck Mediates Activation of Swelling-induced Chloride Channels in Lymphocytes

            Osmotic cell swelling activates Cl− channels to achieve anion efflux. In this study, we find that both the tyrosine kinase inhibitor herbimycin A and genetic knockout of p56 lck , a src-like tyrosine kinase, block regulatory volume decrease (RVD) in a human T cell line. Activation of a swelling-activated chloride current (ICl−swell) by osmotic swelling in whole-cell patch-clamp experiments is blocked by herbimycin A and lavendustin. Osmotic activation of ICl−swell is defective in p56 lck -deficient cells. Retransfection of p56 lck restores osmotic current activation. Furthermore, tyrosine kinase activity is sufficient for activation of ICl−swell. Addition of purified p56 lck to excised patches activates an outwardly rectifying chloride channel with 31 pS unitary conductance. Purified p56 lck washed into the cytoplasm activates ICl−swell in native and p56 lck -deficient cells even when hypotonic intracellular solutions lead to cell shrinkage. When whole-cell currents are activated either by swelling or by p56 lck , slow single-channel gating events can be observed revealing a unitary conductance of 25–28 pS. In accordance with our patch-clamp data, osmotic swelling increases activity of immunoprecipitated p56 lck . We conclude that osmotic swelling activates ICl−swell in lymphocytes via the tyrosine kinase p56 lck .
              • Record: found
              • Abstract: found
              • Article: not found

              Identification of the ankyrin-binding domain of the mouse T-lymphoma cell inositol 1,4,5-trisphosphate (IP3) receptor and its role in the regulation of IP3-mediated internal Ca2+ release.

              In this study we have used several complementary techniques to explore the interaction between the membrane linker molecule, ankyrin, and the inositol 1,4,5-trisphosphate (IP3) receptor in mouse T-lymphoma cells. Using double immunolabeling and laser confocal microscopy, we have found that both cytoplasmic IP3 receptor and ankyrin are preferentially accumulated within ligand-induced lymphocyte receptor-capped structures. The binding between ankyrin and IP3 receptor appears to be very specific. Further analyses indicate that the amino acid sequence GGVGDVLRKPS in the IP3 receptor shares a great deal of structural homology with the ankyrin-binding domain located in certain well characterized ankyrin-binding proteins such as the cell adhesion molecule, CD44. Biochemical studies using competition binding assays and a synthetic peptide identical to GGVGDVLRKPS (a sequence detected in rat brain IP3 receptor (amino acids 2548-2558) and mouse brain IP3 receptor (amino acids 2546-2556)) indicate that this 11-amino acid peptide binds specifically to ankyrin (but not fodrin or spectrin). Furthermore, this peptide competes effectively for ankyrin binding to IP3 receptor-containing vesicles and/or purified IP3 receptor, and it blocks ankyrin-induced inhibitory effects on IP3 binding and IP3-mediated internal Ca2+ release in mouse T-lymphoma cells. These findings suggest that this amino acid sequence, GGVGDVLRKPS, which is located close to the C terminus of the IP3 receptor, resides on the cytoplasmic side (not the luminal side) of IP3 receptor-containing vesicles. This unique region appears to be an important part of the IP3 receptor ankyrin-binding domain and may play an important role in the regulation of IP3 receptor-mediated internal Ca2+ release during lymphocyte activation.

                Author and article information

                S. Karger AG
                December 2000
                01 December 2000
                : 86
                : 4
                : 414-427
                Department of Biophysics, Institute of Cell Physiology, National University of Mexico, Mexico City, Mexico
                45829 Nephron 2000;86:414–427
                © 2000 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
                Tables: 6, References: 174, Pages: 14
                Self URI (application/pdf):
                Seminars in Renal Physiology.<br>Section Editor: F. Lang, Tübingen


                Comment on this article