SEARCH:   Advanced

Blood, 15 March 2007, Vol. 109, No. 6, pp. 2622-2629. Prepublished online as a Blood First Edition Paper on November 30, 2006; DOI 10.1182/blood-2006-03-001404. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2006-03-001404v1 109/6/2622    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Browning, J. A. Articles by Gibson, J. S. Search for Related Content PubMed PubMed Citation Articles by Browning, J. A. Articles by Gibson, J. S. Related Collections Red Cells Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  RED CELLS The effect of deoxygenation on whole-cell conductance of red blood cells from healthy individuals and patients with sickle cell disease Joseph A. Browning1, Henry M. Staines2, Hannah C. Robinson1, Trevor Powell1, J. Clive Ellory1, and John S. Gibson3 1 Department of Physiology, Anatomy and Genetics, University of Oxford, United Kingdom; 2 Department of Cellular and Molecular Medicine–Infectious Diseases, St George's, University of London, United Kingdom; and 3 Department of Veterinary Medicine, University of Cambridge, United Kingdom. Red blood cells from patients with sickle cell disease (SCD) exhibit increased electrogenic cation permeability, particularly following deoxygenation and hemoglobin (Hb) polymerisation. This cation permeability, termed Psickle, contributes to cellular dehydration and sickling, and its inhibition remains a major goal for SCD treatment. Nevertheless, its characteristics remain poorly defined, its molecular identity is unknown, and effective inhibitors have not been established. Here, patch-clamp methodology was used to record whole-cell currents in single red blood cells from healthy individuals and patients with SCD. Oxygenated normal red blood cells had a low membrane conductance, unaffected by deoxygenation. Oxygenated HbS cells had significantly increased conductance and, on deoxygenation, showed a further rise in membrane conductance. The deoxygenation-induced pathway was variable in magnitude. It had equal permeability to Na+ and K+, but was less permeable to NMDG+ and Cl–. Conductance to Ca2+ was also of a similar magnitude to that of monovalent cations. It was inhibited by DIDS (100 µM), Zn2+ (100 µM), and by Gd3+ (IC50 of approximately 2 µM). It therefore shares some properties with Psickle. These findings represent the first electrical recordings of single HbS cells and will facilitate progress in understanding altered red blood cell cation transport characteristics of SCD. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

	Blood Online is supported in part by Genentech BioOncology and Biogen Idec
	Copyright © 2007 by American Society of Hematology         Online ISSN: 1528-0020