A stretch-activated anion channel is up-regulated by the malaria parasite plasmodium falciparum

• Published in: The Journal of physiology Vol. 542; no. 3; pp. 795 - 801
• Main Authors: Egée, Stéphane, Lapaix, Franck, Decherf, Gaëtan, Staines, Henry M., Ellory, J. Clive, Doerig, Christian, Thomas, Serge L. Y.
• Format: Journal Article
• Language: English
• Published: Oxford, UK The Physiological Society 01.08.2002; Blackwell Publishing Ltd; Blackwell Science Inc
• Subjects: Animals; Anions - metabolism; Cells, Cultured; Erythrocytes - metabolism; Erythrocytes - parasitology; Humans; Ion Channels - physiology; Malaria - metabolism; Patch-Clamp Techniques; Physical Stimulation; Plasmodium falciparum - physiology; Rapid Report; Reference Values; Up-Regulation
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2002.022970

A recent study on malaria-infected human red blood cells (RBCs) has shown induced ion channel activity in the host cell membrane, but the questions of whether they are host- or parasite-derived and their molecular nature have not been resolved. Here we report a comparison of a malaria-induced anion channel with an endogenous anion channel in Plasmodium falciparum -infected human RBCs. Ion channel activity was measured using the whole-cell, cell-attached and excised inside-out configurations of the patch-clamp method. Parasitised RBCs were cultured in vitro , using co-cultured uninfected RBCs as controls. Unstimulated uninfected RBCs possessed negligible numbers of active anion channels. However, anion channels could be activated in the presence of protein kinase A (PKA) and ATP in the pipette solution or by membrane deformation. These channels displayed linear conductance (∼15 pS), were blocked by known anion channel inhibitors and showed the permeability sequence I − > Br − > Cl − . In addition, in less than 5 % of excised patches, an outwardly rectifying anion channel (∼80 pS, outward conductance) was spontaneously active. The host membrane of malaria-infected RBCs possessed spontaneously active anion channel activity, with identical conductances, pharmacology and selectivity to the linear conductance channel measured in stimulated uninfected RBCs. Furthermore, the channels measured in malaria-infected RBCs were shown to have a low open-state probability ( P o ) at positive potentials, which explains the inward rectification of membrane conductance observed when using the whole-cell configuration. The data are consistent with the presence of two endogenous anion channels in human RBCs, of which one (the linear conductance channel) is up-regulated by the malaria parasite P. falciparum .