title: Effects of elevated intracellular calcium on the osmotic fragility of human red blood cells.
abstract: High throughput methodologies that measure the distribution of osmotic fragilities in red blood cell populations have enabled the investigation of dynamic changes in red cell homeostasis and membrane permeability in health and disease. The common assumption in the interpretation of dynamic changes in osmotic fragility curves is that left or right shifts reflect a decreased or increased hydration state of the cells, respectively, allowing direct inferences on membrane transport from osmotic fragility measurements. However, the assumed correlation between shifts in osmotic fragility and hydration state has never been directly explored, and may prove invalid in certain conditions. We investigated here whether this correlation holds for red cells exposed to elevated intracellular calcium. The results showed that elevated cell calcium causes a progressive increase in osmotic fragility with minimal contribution from cell hydration (<8%). Loss of membrane area by the release of 160+/-40nm diameter (mean+/-SD) vesicles is shown to be a major contributor, but may not account for the full non-hydration component. The rest must reflect a specific calcium-induced lytic vulnerability of the membrane causing rupture before the cells attain their maximal spherical volumes. The implications of these findings are discussed.
authors: Centre National de la Recherche Scientifique, Université Pierre et Marie Curie Paris, UMR, Roscoff, France.
authors: Anne
authors: A
authors: Cueff
authors: Rachel
authors: R
authors: Seear
authors: Agnieszka
authors: A
authors: Dyrda
authors: Guillaume
authors: G
authors: Bouyer
authors: Stéphane
authors: S
authors: Egée
authors: Alessandro
authors: A
authors: Esposito
authors: Jeremy
authors: J
authors: Skepper
authors: Teresa
authors: T
authors: Tiffert
authors: Virgilio L
authors: VL
authors: Lew
authors: Serge L Y
authors: SL
authors: Thomas
mesh_terms: D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology*; D020013:Calcium Signaling / Q000502:physiology*; D002463:Cell Membrane Permeability / Q000502:physiology*; D048429:Cell Size / Q000187:drug effects; D055252:Cell-Derived Microparticles / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D003022:Clotrimazole / Q000494:pharmacology; D004912:Erythrocytes / Q000378:metabolism* / Q000648:ultrastructure; D006461:Hemolysis / Q000187:drug effects; D057166:High-Throughput Screening Assays; D006801:Humans; D046529:Microscopy, Electron, Transmission; D009996:Osmotic Fragility / Q000187:drug effects; D014867:Water / Q000032:analysis
chemical_list: D014867:Water; D000001:Calcimycin; D003022:Clotrimazole; D002118:Calcium