Electrical conductivity of human erythrocytes infected with Plasmodium falciparum and its modification following quinine therapy (original) (raw)
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Electrophysiological studies of malaria parasite-infected erythrocytes: Current status
International Journal for Parasitology, 2007
The altered permeability characteristics of erythrocytes infected with malaria parasites have been a source of interest for over 30 years. Recent electrophysiological studies have provided strong evidence that these changes reflect transmembrane transport through ion channels in the host erythrocyte plasma membrane. However, conflicting results and differing interpretations of the data have led to confusion in this field. In an effort to unravel these issues, the groups involved recently came together for a week of discussion and experimentation. In this article, the various models for altered transport are reviewed, together with the areas of consensus in the field and those that require a better understanding.
Dielectrophoretic detection of changes in erythrocyte membranes following malarial infection
Biochimica et Biophysica Acta (BBA) - Biomembranes, 1997
The dielectric properties of normal erythrocytes were compared to those of cells infected with the malarial parasite Plasmodium falciparum. Normal cells provided stable electrorotation spectra which, when analyzed by a single-shelled oblate spheroid dielectric model, gave a specific capacitance value of 12 " 1.2 mFrm 2 for the plasma membrane, a cytoplasmic permittivity of 57 " 5.4 and a cytoplasmic conductivity of 0.52 " 0.05 Srm. By contrast, parasitized cells exhibited electrorotation spectra with a time-dependency that suggested significant net ion outflux via the plasma membrane and it was not possible to derive reliable cell parameter values in this case. To overcome this problem, cell membrane dielectric properties were instead determined from dielectrophoretic crossover frequency measurements made as a function of the cell suspending medium conductivity. The crossover frequency for normal cells depended linearly on the suspension conductivity above 20 mSrm and analysis according to the single-shelled oblate spheroid dielectric model yielded values of 11.8 mFrm 2 and 271 Srm 2 , respectively, for the specific capacitance and conductance of the plasma membrane. Unexpectedly, the crossover frequency characteristics of parasitized cells at high suspending medium conductivities were non-linear. This effect was analyzed in terms of possible dependencies of the cell membrane capacitance, conductance or shape on the suspension medium conductivity, and we concluded that variations in the membrane conductance were most likely responsible for the observed non-linearity. According to this model, parasitized cells had a specific membrane capacitance of 9 " 2 mFrm 2 and a specific membrane conductance of 1130 Srm 2 that increased with increasing cell suspending medium conductivity. Such conductivity changes in parasitized cells are discussed in terms of previously observed parasite-associated membrane pores. Finally, we conclude that the large differences between the dielectrophoretic crossover characteristics of normal and parasitized cells should allow straightforward sorting of these cell types by dielectrophoretic methods.
Pflügers Archiv - European Journal of Physiology, 2005
Intraerythrocytic survival of the malaria pathogen Plasmodium falciparum requires delivery of nutrients and disposal of waste products across the host erythrocyte membrane. Recent patch-clamp experiments have demonstrated inwardly and outwardly rectifying anion conductances in infected but not in control erythrocytes. A ClC-2-generated fraction of the inwardly rectifying current is activated by cell swelling and presumably subserves host cell volume regulation. In contrast, the outwardly rectifying current is insensitive to cell volume but allows the passage of lactate and is involved in the transport of nutrients. The present study was performed to characterize the permselectivity and pH sensitivity of the anion conductances using wholecell recording. The outwardly rectifying and the inwardly rectifying currents exhibited permselectivities of Cl À ‡Br À %I À >SCN À and SCN À >I À >Br À >Cl À , respectively, as evident from the reversal potentials recorded under biionic conditions. While the inwardly rectifying current was not affected significantly by alterations of pH between 6.0 and 8.4, the outward rectifier was inhibited strongly by alkalinization to pH ‡7.8. Fluxes of 14 C-lactate and parasite growth were decreased markedly by the increase of bath pH, an effect that may at least in part be due to inhibition of the outward rectifier and subsequently impaired transport across the erythrocyte membrane.
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.
Biosensors and Bioelectronics, 2009
The malaria parasite, Plasmodium falciparum, invades human erythrocytes and induces dramatic changes in the host cell. The idea of this work was to use RBC modified electrode to perform electrochemical impedance spectroscopy (EIS) with the aim of monitoring physiological changes affecting the erythrocyte after invasion by the malaria parasite. Impedance cell-based devices are potentially useful to give insight into cellular behavior and to detect morphological changes. The modelling of impedance plots (Nyquist diagram) in equivalent circuit taking into account the presence of the cellular layer, allowed us pointing out specific events associated with the development of the parasite such as (i) strong changes in the host cell cytoplasm illustrated by changes in the film capacity, (ii) perturbation of the ionic composition of the host cell illustrated by changes in the film resistance, (iii) releasing of reducer (lactic acid or heme) and an enhanced oxygen consumption characterized by changes in the charge transfer resistance and in the Warburg coefficient characteristic of the redox species diffusion. These results show that the RBC-based device may help to analyze strategic events in the malaria parasite development constituting a new tool in antimalarial research.
The Study of Blood Conductivity and Viscosity in Malaria
Physical Science International Journal
Malaria is the most widespread disease in Africa and developing countries which has a negative effect on everyday life and causes thousands death each year. To find new, more precise, and less expensive diagnostic methods, an increasing number of studies are needed. In order to replace the conventional method for detecting the presence of malaria parasites in human blood, the electrical conductivity and viscosity of the blood of falciparum malaria were measured. To investigate the effect of malaria on physical properties; a total of hundred blood samples were collected from Khartoum state teaching hospital, samples were subdivided into two groups, fifty from the malaria patient and other fifty from healthy people setting as control group. An Ostwald viscometer, a hematocrit centrifuge and conductivity equipment were used to measure the viscosity, hematocrit and electrical conductivity of blood respectively. In this study it was found that the mean value of hematocrit for healthy ind...
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.
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