Item type:Thesis, Open Access

Progressive Splenomegalie und Makrozytose bei KCa3.1-defizienten Mäusen: Die physiologische Bedeutung des Gardos-Kanals im Erythrozyten

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Date

2010-12-02

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Philipps-Universität Marburg
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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. 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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Dates
Created: 2010Issued: 2010-12-02Updated: 2011-08-10
DOI
https://doi.org/10.17192/z2010.0682
Faculty
Medizin
Publisher
Philipps-Universität Marburg
Language
ger
Data types
DoctoralThesis
Keywords
Osmotic stressErythrocytesSplenomegalyCa2+activated potassium channelFilterability
DFG-subjects
Ca2+-aktivierter Kalium-Kanal, ErythrozytenFitrierbarkeitSplenomegalieOsmotischer StressGardos-Kanal
DDC-Numbers
610
License
https://rightsstatements.org/vocab/InC-NC/1.0/
URI
https://open.uni-marburg.de/handle/10.17192/z2010.0682
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Paschen, Steffen: Progressive Splenomegalie und Makrozytose bei KCa3.1-defizienten Mäusen: Die physiologische Bedeutung des Gardos-Kanals im Erythrozyten. : Philipps-Universität Marburg 2010-12-02. DOI: https://doi.org/10.17192/z2010.0682.

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