Plasmodium Induces Swelling-activated ClC-2 Anion Channels in the Host Erythrocyte

Plasmodium Induces Swelling-activated ClC-2 Anion Channels in the Host Erythrocyte

Intraerythrocytic growth of the human malaria parasite Plasmodium falciparum depends on delivery of nutrients. Moreover, infection challenges cell volume constancy of the host erythrocyte requiring enhanced activity of cell volume regulatory mechanisms. Patch clamp recording demonstrated inwardly an...

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Bibliographic Details
Published in:The Journal of biological chemistry 2004-10, Vol.279 (40), p.41444-41452
Main Authors: Huber, Stephan M, Duranton, Christophe, Henke, Guido, Van De Sand, Claudia, Heussler, Volker, Shumilina, Ekaterina, Sandu, Ciprian D, Tanneur, Valerie, Brand, Verena, Kasinathan, Ravi S, Lang, Karl S, Kremsner, Peter G, Hübner, Christian A, Rust, Marco B, Dedek, Karin, Jentsch, Thomas J, Lang, Florian
Format: Article
Language:eng
Subjects:
Animals
Cell Membrane Permeability
Cell Size
Chloride Channels - biosynthesis
Chloride Channels - metabolism
Erythrocytes - cytology
Erythrocytes - metabolism
Erythrocytes - parasitology
Gene Expression Regulation
Humans
Mice
Mice, Knockout
Osmosis
Patch-Clamp Techniques
Plasmodium berghei
Plasmodium berghei - growth & development
Plasmodium berghei - physiology
Plasmodium falciparum
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Summary:Intraerythrocytic growth of the human malaria parasite Plasmodium falciparum depends on delivery of nutrients. Moreover, infection challenges cell volume constancy of the host erythrocyte requiring enhanced activity of cell volume regulatory mechanisms. Patch clamp recording demonstrated inwardly and outwardly rectifying anion channels in infected but not in control erythrocytes. The molecular identity of those channels remained elusive. We show here for one channel type that voltage dependence, cell volume sensitivity, and activation by oxidation are identical to ClC-2. Moreover, Western blots and FACS analysis showed protein and functional ClC-2 expression in human erythrocytes and erythrocytes from wild type ( Clcn2 +/+ ) but not from Clcn2 –/– mice. Finally, patch clamp recording revealed activation of volume-sensitive inwardly rectifying channels in Plasmodium berghei -infected Clcn2 +/+ but not Clcn2 –/– erythrocytes. Erythrocytes from infected mice of both genotypes differed in cell volume and inhibition of ClC-2 by ZnCl 2 (1 m m ) induced an increase of cell volume only in parasitized Clcn2 +/+ erythrocytes. Lack of ClC-2 did not inhibit P. berghei development in vivo nor substantially affect the mortality of infected mice. In conclusion, activation of host ClC-2 channels participates in the altered permeability of Plasmodium -infected erythrocytes but is not required for intraerythrocytic parasite survival.
ISSN:0021-9258
1083-351X