A stretch-activated anion channel is up-regulated by the malaria parasite Plasmodium falciparum.
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.
Egée
Stéphane
S
Centre National de la Recherche Scientifique, UPR 9042, Station Biologique, Place G.Teissier, B. P. 74, 29682 Roscoff cedex, France.
Lapaix
Franck
F
Decherf
Gaëtan
G
Staines
Henry M
HM
Ellory
J Clive
JC
Doerig
Christian
C
Thomas
Serge L Y
SL
D000818:Animals; D000838:Anions / Q000378:metabolism*; D002478:Cells, Cultured; D004912:Erythrocytes / Q000378:metabolism* / Q000469:parasitology*; D006801:Humans; D007473:Ion Channels / Q000502:physiology*; D008288:Malaria / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010812:Physical Stimulation; D010963:Plasmodium falciparum / Q000502:physiology*; D012016:Reference Values; D015854:Up-Regulation
D000838:Anions; D007473:Ion Channels