Association between morphologic distortion of sickle cells and deoxygenation-induced cation permeability increase

We hypothesized that the deoxygenation-induced increase in cation permeability of sickle cells was related to mechanical distention of the membrane by growing HbS polymer within the cell. To test this hypothesis, we determined the effect of deoxygenation on cation fluxes in sickle cells under conditions that restricted or permitted extensive growth of polymer, producing different degrees of membrane distention. Manipulation of suspending medium osmolality for density-isolated high and low mean cell hemoglobin concentration (MCHC) cells was used to regulate the extensional growth of polymer bundles and hence membrane distortion. For initially low MCHC cells, the deoxygenation-induced increase in both Na and K fluxes was markedly suppressed when the MCHC was increased by increasing the osmolality. This suppression corresponded to the inhibition of extensive morphologic cellular distortion. For initially high MCHC, ISC-rich cells, deoxygenation had minimal effect on K permeability. However, reduction of MCHC by a decrease in osmolality produced a concomitant increase in cation permeability and cellular distortion. These observations support the idea that the sickling-associated increase in membrane permeability is related to mechanical stress imposed on the membrane by bundles of HbS polymer.