title: A two-compartment model of osmotic lysis in Plasmodium falciparum-infected erythrocytes.
abstract: We recently identified a voltage-dependent anion channel on the surface of human red blood cells (RBCs) infected with the malaria parasite, Plasmodium falciparum. This channel, the plasmodial erythrocyte surface anion channel (PESAC), likely accounts for the increased permeability of infected RBCs to various small solutes, as assessed quantitatively with radioisotope flux and patch-clamp studies. Whereas this increased permeability has also been studied by following osmotic lysis of infected cells in permeant solutes, these experiments have been limited to qualitative comparisons of lysis rates. To permit more quantitative examination of lysis rates, we have developed a mathematical model for osmotic fragility of infected cells based on diffusional uptake via PESAC and the two-compartment geometry of infected RBCs. This model, combined with a simple light scattering assay designed to track osmotic lysis precisely, produced permeability coefficients that match both previous isotope flux and patch-clamp estimates. Our model and light scattering assay also revealed Michaelian kinetics for inhibition of PESAC by furosemide, suggesting a 1:1 stoichiometry for their interaction.
authors.affiliation: Molecular Physiology Unit, Laboratory of Malaria and Vector Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Marissa A
authors.initials: MA
authors.lastname: Wagner
authors.forename: Biree
authors.initials: B
authors.lastname: Andemariam
authors.forename: Sanjay A
authors.initials: SA
authors.lastname: Desai
mesh_terms: D000818:Animals; D002463:Cell Membrane Permeability; D002478:Cells, Cultured; D003198:Computer Simulation; D004910:Erythrocyte Membrane / Q000187:drug effects / Q000378:metabolism* / Q000469:parasitology*; D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology; D005665:Furosemide / Q000494:pharmacology; D006461:Hemolysis; D006801:Humans; D015640:Ion Channel Gating / Q000187:drug effects; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D016778:Malaria, Falciparum / Q000097:blood / Q000378:metabolism / Q000469:parasitology; D008954:Models, Biological; D008956:Models, Chemical; D009995:Osmosis; D009997:Osmotic Pressure; D010963:Plasmodium falciparum / Q000469:parasitology* / Q000502:physiology; D012680:Sensitivity and Specificity; D013012:Sorbitol / Q000378:metabolism; D013053:Spectrophotometry / Q000379:methods
chemical_list: D007473:Ion Channels; C505335:surface anion channel protein, Plasmodium falciparum; D013012:Sorbitol; D005665:Furosemide