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Received April 22, 2002
Accepted after revision June 11, 2002
1 Centre National de la Recherche Scientifique, UPR 9042, Station Biologique, Place G.Teissier, B. P. 74, 29682 Roscoff cedex, France, University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK and INSERM U511, CHU Pitié-Salpètriére, 91 Bd. de l'Hôpital, 75634 Paris cedex 13, France
2 Centre National de la Recherche Scientifique, UPR 9042, Station Biologique, Place G.Teissier, B. P. 74, 29682 Roscoff cedex, France
* To whom correspondence should be addressed. E-mail: thomas{at}sb-roscoff.fr.
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 (Po) 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.
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