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O 2 dependence of K + transport in sickle cells: the effect of different cell populations and the substituted benzaldehyde 12C79
Author(s) -
GIBSON J. S.,
KHAN A,
SPEAKE P. F.,
ELLORY J. C.
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0177com
Subject(s) - cotransporter , chemistry , cell , pathophysiology , population , red cell , benzaldehyde , biophysics , biochemistry , medicine , endocrinology , biology , organic chemistry , catalysis , environmental health , sodium
The molecular basis of sickle cell disease (SCD) is well known but the pathophysiology is poorly understood. It remains intractable to therapy. Hyperactivity of several membrane transport systems, including the K + ‐Cl − cotransporter (termed KCC), cause HbS‐containing red cells (termed HbS cells) to dehydrate and sickle, leading to the development of sickle cell crises (SCCs). Contrary to normal red cells (HbA cells), KCC in HbS cells is active at low O 2 tensions ( PO 2 s), remaining responsive to low pH or urea. Since these stimuli are usually encountered in hypoxic regions, the abnormal O 2 dependence increases the contribution of KCC to dehydration, and hence development of SCCs. These differences with HbA cells may be due to the younger population of cells or to polymerization of HbS. We used 86 Rb + asaK + congener to investigate the activity of KCC at different PO 2 s, and density gradient separation to investigate different red cell fractions. We found no correlation of O 2 dependence with cell fractions. We also used the substituted benzaldehyde 12C79 to increase the O 2 affinity of HbS and found that its effect on HbS O 2 saturation and cell sickling correlated with that on both Cl − ‐independent and Cl − ‐dependent K + transport, implying that, at low PO 2 s, KCC activity correlated with HbS polymerization. The importance of these results to understanding the pathophysiology of SCD, and for the design of chemo‐therapeutic agents to ameliorate or prevent SCC, is discussed.—Gibson, J. S., Khan, A., Speake, P. F., Ellory, J. C. O 2 dependence of K + transport in sickle cells: the effect of different cell populations and the substituted benzaldehyde 12C79. FASEB J. 15, 823‐832 (2001)