Toward a unifying model of malaria-induced channel activity.
Infection of RBC by the malaria parasite Plasmodium falciparum activates, at the trophozoite stage, a membrane current 100- to 150-fold larger than in uninfected RBC. This current is carried by small anion channels initially described in supraphysiological ion concentrations (1.115 M Cl(-)) and named plasmodial surface anion channels (PSAC), suggesting their plasmodial origin. Our results obtained with physiological ion concentrations (0.145 M Cl(-)) support the notion that the parasite-induced channels represent enhanced activity versions of anion channels already present in uninfected RBCs. Among them, an 18-pS inwardly rectifying anion channel (IRC) and a 4- to 5-pS small conductance anion channel (SCC) were present in most single-channel recordings of infected membranes. The aim of this study was to clarify disparities in the reported electrophysiological data and to investigate possible technical reasons why these discrepancies have arisen. We demonstrate that PSAC is the supraphysiological correlate of the SCC and is inhibited by Zn(2+), suggesting that it is a ClC-2 channel. We show that in physiological solutions 80% of the membrane conductance in infected cells can be accounted for by IRC and 20% can be accounted for by SCC whereas in supraphysiological conditions the membrane conductance is almost exclusively carried by SCC (PSAC) because the IRC is functionally turned off.
Bouyer
Guillaume
G
Laboratory of Cell Physiology of Erythrocytes, Centre National de la Recherche Scientifique, Université Pierre et Marie Curie, Unité Mixte de Recherche 7150, Station Biologique, B.P. 74, 29682 Roscoff Cedex, France.
Egée
Stéphane
S
Thomas
Serge L Y
SL
D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; D018118:Chloride Channels / Q000378:metabolism; D004553:Electric Conductivity; D004594:Electrophysiology; D004912:Erythrocytes / Q000469:parasitology / Q000473:pathology; D006801:Humans; D007473:Ion Channels / Q000378:metabolism* / Q000503:physiopathology; D008288:Malaria / Q000503:physiopathology*; D008954:Models, Biological; D010963:Plasmodium falciparum / Q000472:pathogenicity
D018118:Chloride Channels; D007473:Ion Channels; C505335:surface anion channel protein, Plasmodium falciparum