SEARCH:   Advanced

Blood, 1 January 2005, Vol. 105, No. 1, pp. 361-367. Prepublished online as a Blood First Edition Paper on August 31, 2004; DOI 10.1182/blood-2004-01-0125. This Article Full Text (PDF) All Versions of this Article: 2004-01-0125v1 105/1/361    most recent Alert me when this article is cited Alert me if a correction is posted 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 HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Lew, V. L Articles by Bookchin, R. M Search for Related Content PubMed PubMed Citation Articles by Lew, V. L Articles by Bookchin, R. M Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 13, 2004 Accepted July 10, 2004 Distribution of dehydration rates generated by maximal Gardos channel activation in normal and sickle red blood cells Virgilio L Lew*, Teresa Tiffert, Zipora Etzion, Deisy Perdomo, Nuala Daw, Lynn Macdonald, and Robert M Bookchin Physiological Laboratory, University of Cambridge, Cambridge, United Kingdom Department of Medicine, Albert Einstein College of Medicine, Bronx, NY, USA * Corresponding author; email: vll1{at}cam.ac.uk. The Ca2+-activated K+ channels of human red blood cells (RBCs) (Gardos channels, hIK1, hSK4) can mediate rapid cell dehydration, of particular relevance to the pathophysiology of sickle cell disease. Previous investigations gave widely discrepant estimates of the number of Gardos channels per RBC, from 1-3 to 300, with large cell-to-cell differences, suggesting that RBCs could differ extensively in their susceptibility to dehydration by elevated Ca2+. Here we investigated the distribution of dehydration rates induced by maximal and uniform Ca2+ loads in normal (AA) and sickle (SS) RBCs by measuring the time-dependent changes in osmotic fragility and RBC volume distributions. We found a remarkable conservation of osmotic lysis and volume distribution profiles during Ca2+-induced dehydration, indicating overall uniformity of dehydration rates among both AA and SS RBCs. In the light of these results, alternative interpretations were suggested for the previously proposed low estimates and heterogeneity of channel numbers per cell. The results support the view that stochastic Ca2+ permeabilization rather than Gardos channel variation is the main determinant selecting which SS cells dehydrate via Gardos channels in each sickling episode. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: T. Tiffert, N. Daw, Z. Etzion, R. M. Bookchin, and V. L. Lew Age Decline in the Activity of the Ca2+-sensitive K+ Channel of Human Red Blood Cells J. Gen. Physiol., April 30, 2007; 129(5): 429 - 436. [Abstract] [Full Text] [PDF] J. A. Browning, H. M. Staines, H. C. Robinson, T. Powell, J. C. Ellory, and J. S. Gibson The effect of deoxygenation on whole-cell conductance of red blood cells from healthy individuals and patients with sickle cell disease Blood, March 15, 2007; 109(6): 2622 - 2629. [Abstract] [Full Text] [PDF]

	Copyright © 2004 by American Society of Hematology         Online ISSN: 1528-0020