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Volume 2011, Article ID 379894, 8 pages
Research Article

Role of Calcium in Phosphatidylserine Externalisation in Red Blood Cells from Sickle Cell Patients

1Department of Veterinary Medicine, University of Cambridge, Madingley Road, Cambridge CB3 0ES, UK
2Department of Molecular Haematology, King's College School of Medicine, London SE5 9RS, UK

Received 13 July 2010; Accepted 23 August 2010

Academic Editor: Ferreira Costa

Copyright © 2011 Erwin Weiss et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Phosphatidylserine exposure occurs in red blood cells (RBCs) from sickle cell disease (SCD) patients and is increased by deoxygenation. The mechanisms responsible remain unclear. RBCs from SCD patients also have elevated cation permeability, and, in particular, a deoxygenation-induced cation conductance which mediates C a 2 + entry, providing an obvious link with phosphatidylserine exposure. The role of C a 2 + was investigated using FITC-labelled annexin. Results confirmed high phosphatidylserine exposure in RBCs from SCD patients increasing upon deoxygenation. When deoxygenated, phosphatidylserine exposure was further elevated as extracellular [ C a 2 + ] was increased. This effect was inhibited by dipyridamole, intracellular C a 2 + chelation, and Gardos channel inhibition. Phosphatidylserine exposure was reduced in high K + saline. C a 2 + levels required to elicit phosphatidylserine exposure were in the low micromolar range. Findings are consistent with C a 2 + entry through the deoxygenation-induced pathway ( P s i c k l e ), activating the Gardos channel. [ C a 2 + ] required for phosphatidylserine scrambling are in the range achievable in vivo.