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Effects of deoxygenation on active and passive Ca2+ transport and on the cytoplasmic Ca2+ levels of sickle cell anemia red cells.
J Clin Invest 1993; 92(5):2489-98JCI

Abstract

Elevated [Ca2+]i in deoxygenated sickle cell anemia (SS) red cells (RBCs) could trigger a major dehydration pathway via the Ca(2+)-sensitive K+ channel. But apart from an increase in calcium permeability, the effects of deoxygenation on the Ca2+ metabolism of sickle cells have not been previously documented. With the application of 45Ca(2+)-tracer flux methods and the combined use of the ionophore A23187, Co2+ ions, and intracellular incorporation of the Ca2+ chelator benz-2, in density-fractionated SS RBCs, we show here for the first time that upon deoxygenation, the mean [Ca2+]i level of SS discocytes was significantly increased, two- to threefold, from a normal range of 9.4 to 11.4 nM in the oxygenated cells, to a range of 21.8 to 31.7 nM in the deoxygenated cells, closer to K+ channel activatory levels. Unlike normal RBCs, deoxygenated SS RBCs showed a two- to fourfold increase in pump-leak Ca2+ turnover. Deoxygenation of the SS RBCs reduced their Ca2+ pump Vmax, more so in reticulocyte- and discocyte-rich than in dense cell fractions, and decreased their cytoplasmic Ca2+ buffering. Analysis of these results suggests that both increased Ca2+ influx and reduced Ca2+ pump extrusion contribute to the [Ca2+]i elevation.

Authors+Show Affiliations

Department of Medicine, Albert Einstein College of Medicine, Bronx, New York 10461.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

8227363

Citation

Etzion, Z, et al. "Effects of Deoxygenation On Active and Passive Ca2+ Transport and On the Cytoplasmic Ca2+ Levels of Sickle Cell Anemia Red Cells." The Journal of Clinical Investigation, vol. 92, no. 5, 1993, pp. 2489-98.
Etzion Z, Tiffert T, Bookchin RM, et al. Effects of deoxygenation on active and passive Ca2+ transport and on the cytoplasmic Ca2+ levels of sickle cell anemia red cells. J Clin Invest. 1993;92(5):2489-98.
Etzion, Z., Tiffert, T., Bookchin, R. M., & Lew, V. L. (1993). Effects of deoxygenation on active and passive Ca2+ transport and on the cytoplasmic Ca2+ levels of sickle cell anemia red cells. The Journal of Clinical Investigation, 92(5), pp. 2489-98.
Etzion Z, et al. Effects of Deoxygenation On Active and Passive Ca2+ Transport and On the Cytoplasmic Ca2+ Levels of Sickle Cell Anemia Red Cells. J Clin Invest. 1993;92(5):2489-98. PubMed PMID: 8227363.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of deoxygenation on active and passive Ca2+ transport and on the cytoplasmic Ca2+ levels of sickle cell anemia red cells. AU - Etzion,Z, AU - Tiffert,T, AU - Bookchin,R M, AU - Lew,V L, PY - 1993/11/1/pubmed PY - 1993/11/1/medline PY - 1993/11/1/entrez SP - 2489 EP - 98 JF - The Journal of clinical investigation JO - J. Clin. Invest. VL - 92 IS - 5 N2 - Elevated [Ca2+]i in deoxygenated sickle cell anemia (SS) red cells (RBCs) could trigger a major dehydration pathway via the Ca(2+)-sensitive K+ channel. But apart from an increase in calcium permeability, the effects of deoxygenation on the Ca2+ metabolism of sickle cells have not been previously documented. With the application of 45Ca(2+)-tracer flux methods and the combined use of the ionophore A23187, Co2+ ions, and intracellular incorporation of the Ca2+ chelator benz-2, in density-fractionated SS RBCs, we show here for the first time that upon deoxygenation, the mean [Ca2+]i level of SS discocytes was significantly increased, two- to threefold, from a normal range of 9.4 to 11.4 nM in the oxygenated cells, to a range of 21.8 to 31.7 nM in the deoxygenated cells, closer to K+ channel activatory levels. Unlike normal RBCs, deoxygenated SS RBCs showed a two- to fourfold increase in pump-leak Ca2+ turnover. Deoxygenation of the SS RBCs reduced their Ca2+ pump Vmax, more so in reticulocyte- and discocyte-rich than in dense cell fractions, and decreased their cytoplasmic Ca2+ buffering. Analysis of these results suggests that both increased Ca2+ influx and reduced Ca2+ pump extrusion contribute to the [Ca2+]i elevation. SN - 0021-9738 UR - https://www.unboundmedicine.com/medline/citation/8227363/Effects_of_deoxygenation_on_active_and_passive_Ca2+_transport_and_on_the_cytoplasmic_Ca2+_levels_of_sickle_cell_anemia_red_cells_ L2 - https://doi.org/10.1172/JCI116857 DB - PRIME DP - Unbound Medicine ER -