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Stochastic nature and red cell population distribution of the sickling-induced Ca2+ permeability.
V L Lew, … , O E Ortiz, R M Bookchin
V L Lew, … , O E Ortiz, R M Bookchin
Published June 1, 1997
Citation Information: J Clin Invest. 1997;99(11):2727-2735. https://doi.org/10.1172/JCI119462.
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Research Article

Stochastic nature and red cell population distribution of the sickling-induced Ca2+ permeability.

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Abstract

To explore basic properties of the sickling-induced cation permeability pathway, the Ca2+ component (Psickle-Ca) was studied in density-fractionated sickle cell anemia (SS) discocytes through its effects on the activity of the cells' Ca2+sensitive K+-channels (KCa). The instant state of KCa channel activation was monitored during continuous or cyclic deoxygenation of the cells using a novel thiocyanate-densecell formation method. Each deoxy pulse caused a reversible, sustained Psickle-Ca, which activated KCa channels in only 10-45% of cells at physiological [Ca2+]o ("activated cells"). After removal of cells activated by each previous deoxy pulse, subsequent pulses generated similar activated cell fractions, indicating a random determination rather than the response of a specific vulnerable subpopulation. The fraction of activated cells rose monotonically with [Ca2+]o along a curve reflecting the cells' distribution of Psickle-Ca, with values high enough in a small cell fraction to trigger near-maximal KCa channels. Consistent with the stochastic nature of Psickle-Ca, repeated deoxygenated-oxygenated pulsing led to progressive dense cell formation, whereas single long pulses caused one early density shift. Thus deoxygenation-induced Ca2+-permeabilization in SS cells is a probabilistic event with large cumulative dehydrating potential. The possible molecular nature of Psickle-Ca is discussed.

Authors

V L Lew, O E Ortiz, R M Bookchin

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