Alteration of the mechanical properties of sickle cells by repetitive deoxygenation: role of calcium and the effects of calcium blockers.
The formation of dense, poorly deformable sickle cells was studied by subjecting pre-separated, less dense cells to repeated deoxygenation and reoxygenation for 15 h. In the presence of Ca (2 mmol/l), this process caused the number of irreversible sickled cells to increase five-fold, mean cell haemoglobin concentration to increase by 13% and cellular potassium to decrease by 22%. Also, red cell filterability through 5 microns filter pores was greatly worsened. These effects decreased but were not totally abolished when the extracellular Ca concentration was lowered to zero or 0.01 mmol/l. If a high K medium was used (135 mmol/l), cell swelling rather than shrinkage occurred. Swelling also occurred if ouabain was added to the incubation. The Ca-channel blockers nitrendipine and nisoldipine had different effects. Nitrendipine, in the range 10(-7) - 10(-5) mol/l, was partially protective against all the induced changes, but nisoldipine was not protective at 10(-8) or 10(-6) mol/l. Thus, deterioration in the properties of sickle cells appears to be linked to Ca-dependent potassium loss during repeated sickling and is inhibited by nitrendipine.
Department of Haematology, St George's Hospital Medical School, London.
G B
GB
Nash
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S
Boghossian
J
J
Parmar
J A
JA
Dormandy
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D
Bevan
D000755:Anemia, Sickle Cell / Q000097:blood*; D002118:Calcium / Q000494:pharmacology*; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004907:Erythrocyte Deformability / Q000187:drug effects; D004913:Erythrocytes, Abnormal / Q000187:drug effects*; D006801:Humans; D009568:Nitrendipine / Q000494:pharmacology; D010100:Oxygen / Q000494:pharmacology*; D011188:Potassium / Q000097:blood; D012964:Sodium / Q000097:blood; D013997:Time Factors
D002121:Calcium Channel Blockers; D009568:Nitrendipine; D012964:Sodium; D011188:Potassium; D010100:Oxygen; D002118:Calcium