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Disruption of the Gardos channel (KCa3.1) in mice causes subtle erythrocyte macrocytosis and progressive splenomegaly

  • Ion Channels, Receptors and Transporters
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

Gardos channel, the erythrocyte Ca2+-activated K+ channel (KCa3.1), is considered a major regulator of red blood cell (RBC) volume by mediating efflux of potassium and thus cell dehydration and shrinkage. However, the functional importance of KCa3.1 in RBC in vivo is incompletely understood. Here, we used KCa3.1−/−-mice to investigate the consequences of KCa3.1 deficiency for RBC indices, functions, and sequestration. RBCs of KCa3.1−/−-mice of all ages were mildly macrocytic but their biconcave appearance being preserved. RBC number, total hemoglobin, and hematocrit were unchanged in the adult KCa3.1−/−-mice and increased in the premature KCa3.1−/−-mice. Filterability, Ca2+-dependent volume decrease and osmotic tolerance of RBCs lacking KCa3.1 were noticeably reduced when compared to RBC of wild-type littermates. Deformability to increasing shear stress was unchanged. Strikingly, KCa3.1−/−-mice developed progressive splenomegaly which was considerable (∼200% of controls) in the >6-month-old mice and was paralleled by increased iron deposition in the aged mice presumably as a consequence of enhanced RBC sequestration. Daily injections of the KCa3.1-blocker TRAM-34 (120 mg/kg) also produced mild splenomegaly in wild-type mice. We conclude that genetic deficit of erythroid KCa3.1 causes mild RBC macrocytosis, presumably leading to reduced filterability, and impairs volume regulation. These RBC defects result in mild but progressive splenomegaly.

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Acknowledgments

This work was supported by the DFG (project-A11-SFB593; J.H., RK.), by the DFG graduate school GRK767 (H.P.E.), and by the German Kidney Foundation and German Society of Hypertension (I.G.). We wish to thank Mrs. Brigitte Agricola for the excellent technical assistance.

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Authors and Affiliations

  1. Department of Internal Medicine—Nephrology, Faculty of Medicine, Philipps-University, 35033, Marburg, Germany

    Ivica Grgic, Brajesh P. Kaistha, Steffen Paschen, Anuradha Kaistha, Christoph Busch, Joachim Hoyer & Ralf Köhler

  2. Division of Nephrology, Albert Einstein College of Medicine, Bronx, NY, USA

    Han Si

  3. Institute of Veterinary Pathology, Justus-Liebig University Giessen, 35392, Giessen, Germany

    Kernt Köhler

  4. Institute for Cytobiology, Philipps-University, 35037, Marburg, Germany

    Hans-Peter Elsässer

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  1. Ivica Grgic
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  9. Joachim Hoyer
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Correspondence to Ralf Köhler.

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Ivica Grgic and Brajesh P. Kaistha contributed equally to this study.

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Grgic, I., Kaistha, B.P., Paschen, S. et al. Disruption of the Gardos channel (KCa3.1) in mice causes subtle erythrocyte macrocytosis and progressive splenomegaly. Pflugers Arch - Eur J Physiol 458, 291–302 (2009). https://doi.org/10.1007/s00424-008-0619-x

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