title: The evolution of the new permeability pathways in Plasmodium falciparum--infected erythrocytes--a kinetic analysis.
abstract: Malaria parasites demonstrably increase the permeability of the membrane of the erythrocyte in which they develop and propagate. New permeability pathways (NPPs) generated by parasite activity and identified in the erythrocyte membrane are held responsible for these changes. Here, we present a novel analysis of hemolysis curves of infected cells in iso-osmotic solutions of solutes that penetrate selectively into infected cells, as a function of parasite development. The analysis yields three parameters: the t(1/2) of lysis (reciprocally related to permeability), the maximal lysis, and a parameter that expresses the variation of the cell population. Different developmental stages of the parasite were obtained either by sampling synchronized cultures with time or by the fractionation of asynchronous cultures on a Percoll-sorbitol density gradient. While the results confirm previous reports on the stage-dependent evolution of NPPs, they also reveal that the evolution of NPPs is not synchronous: NPPs evolve differentially throughout the ring stage and only at the mid-trophozoite stage they are fully deployed in the majority of the infected cells, but not in all. This leads to desynchronization in the culture and to less than the maximal possible rate of multiplication.
authors.affiliation: Department of Biological Chemistry, Institute of Life Sciences, The Hebrew University of Jerusalem, Jerusalem 91904, Israel.
authors.forename: Miriam
authors.initials: M
authors.lastname: Krugliak
authors.forename: Hagai
authors.initials: H
authors.lastname: Ginsburg
mesh_terms: D000818:Animals; D002463:Cell Membrane Permeability / Q000502:physiology*; D002499:Centrifugation, Density Gradient; D004910:Erythrocyte Membrane / Q000378:metabolism* / Q000469:parasitology; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D006454:Hemoglobins / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D017711:Nonlinear Dynamics; D010963:Plasmodium falciparum / Q000254:growth & development / Q000378:metabolism*; D011205:Povidone; D012044:Regression Analysis; D012822:Silicon Dioxide; D013012:Sorbitol
chemical_list: D006454:Hemoglobins; D007202:Indicators and Reagents; D013012:Sorbitol; C016039:Percoll; D012822:Silicon Dioxide; D011205:Povidone