Electrophysiological studies of malaria parasite-infected erythrocytes: Current status (original) (raw)
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Biochimica Et Biophysica Acta-biomembranes, 1982
During the intraerythrocytic growth of Plasmodium falciparmn in culture, marked changes are observed in the permeability properties of the host cell membrane. Anionic substances otherwise impermeant to normal cells, become highly permeant to infected cells. These changes in permeability become apparent as rings mature into trophozoites and remain throughout schizogony. The permeability changes to anionic substances are not manifested as degradation of band 3, the purported erythrocyte anion transporter. They probably reflect alterations of a more general nature.
Transport processes in Plasmodium falciparum-infected erythrocytes: potential as new drug targets
International journal for …, 2002
Plasmodium falciparum infection induces alterations in the transport properties of infected erythrocytes that have recently been defined using electrophysiological techniques. Mechanisms responsible for transport of substrates into intraerythrocytic parasites have also been clarified by studies of three substrate-specific (hexose, nucleoside and aquaglyceroporin) parasite plasma membrane transporters. These have been characterised functionally using the Xenopus laevis oocyte heterologous expression system. The same expression system is currently being used to define the function of parasite 'P' type ATPases responsible for intraparasitic [Ca 21 ] homeostasis. We review studies on these transport processes and examine their potential as novel drug targets. q
Increased permeability of the malaria-infected erythrocyte to organic cations
Biochimica et Biophysica Acta (BBA) - Biomembranes, 2000
The human malaria parasite, Plasmodium falciparum, induces in the plasma membrane of its host red blood cell new permeation pathways (NPP) that allow the influx of a variety of low molecular weight solutes. In this study we have demonstrated that the NPP confer upon the parasitised erythrocyte a substantial permeability to a range of monovalent organic (quaternary ammonium) cations, the largest having an estimated minimum cross-sectional diameter of 11^12 A î . The rate of permeation of these cations showed a marked dependence on the nature of the anion present, increasing with the lyotropicity of the anion. There was no clear relationship between the permeation rate and either the size or the hydrophobicity of these solutes. However, the data were consistent with the rate of permeation being influenced by a combination of these two factors, with the pathways showing a marked preference for the relatively small and hydrophobic phenyltrimethylammonium ion over larger or less hydrophobic solutes. Large quaternary ammonium cations inhibited flux via the NPP, as did long-chain n-alkanols. For both classes of compound the inhibitory potency increased with the size and hydrophobicity of the solute. This study extends the range of solutes known to permeate the NPP of malaria-infected erythrocytes as well as providing some insight into the factors governing the rate of permeation. ß
Organic Osmolyte Permeabilities of the Malaria-induced Anion Conductances in Human Erythrocytes
The Journal of General Physiology, 2004
Infection of human erythrocytes with the malaria parasite Plasmodium falciparum induces new permeability pathways (NPPs) in the host cell membrane. Isotopic flux measurements demonstrated that the NPP are permeable to a wide variety of molecules, thus allowing uptake of nutrients and release of waste products. Recent patchclamp recordings demonstrated the infection-induced up-regulation of an inwardly and an outwardly rectifying Cl Ϫ conductance. The present experiments have been performed to explore the sensitivity to cell volume and the organic osmolyte permeability of the two conductances. It is shown that the outward rectifier has a high relative lactate permeability (P lactate /P Cl ϭ 0.4). Sucrose inhibited the outward-rectifier and abolished the infection-induced hemolysis in isosmotic sorbitol solution but had no or little effect on the inward-rectifier. Furosemide and NPPB blocked the outward-rectifying lactate current and the sorbitol hemolysis with IC 50 s in the range of 0.1 and 1 M, respectively. In contrast, the IC 50 s of NPPB and furosemide for the inward-rectifying current were Ͼ 10 M. Osmotic cell-shrinkage inhibited the inwardly but not the outwardly rectifying conductance. In conclusion, the parasite-induced outwardlyrectifying anion conductance allows permeation of lactate and neutral carbohydrates, whereas the inward rectifier seems largely impermeable to organic solutes. All together, these data should help to resolve ongoing controversy regarding the number of unique channels that exist in P. falciparum -infected erythrocytes.
Molecular Microbiology, 2006
The intraerythrocytic developmental stages of the malaria parasite Plasmodium falciparum are responsible for the clinical symptoms associated with malaria tropica. The non-infected human erythrocyte is a terminally differentiated cell that is unable to synthesize proteins and lipids de novo , and it is incapable of importing a number of solutes that are essential for parasite proliferation. Approximately 12-15 h after invasion the parasitized cell undergoes a marked increase in its permeability to a variety of different solutes present in the extracellular milieu. The increase is due to the induction in the erythrocyte membrane of 'new permeability pathways' which have been characterized in some detail in terms of their transport and electrophysiological properties, but which are yet to be defined at a molecular level. Here we show that these pathways are resistant to trypsin but are abolished by treatment of intact infected erythrocytes with chymotrypsin. On resuspension of chymotrypsinized cells in chymotrypsin-free medium the pathways progressively reappear, a process that can be inhibited by cytotoxic agents, and by brefeldin A which inhibits protein secretion. Our results provide evidence for the involvement of parasite encoded proteins in the generation of the pathways, either as components of the pathways themselves or as auxiliary factors.
Molecular and Biochemical Parasitology, 1985
The host cell membrane of Plasmodiumfalciparum infected cells becomes permeabilized at the trophozoite stage. A variety of otherwise impermeant substances such as carbohydrates, polyols, amino acids and anions easily gain access to the cytosol of infected cells. Using the isotonic-hemolysis method or uptake of labeled substances, we characterized the new permeation pathways as pores of approximately 0.7 nm equivalent radius. The pores bear a positively charged character which facilitates movement of small anions and excludes cations, so that the ionic composition and osmotic properties of infected cells are not drastically altered. Substances of a molecular size similar to that of disaccharides are fully excluded. Substances of limiting size might be accommodated in the pore, provided they bear a side group of hydrophobic character. The new permeation pathways may provide a vital route for acquisition or release of essential nutrients or catabolites.