Journal
BLOOD
Volume 105, Issue 1, Pages 361-367Publisher
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2004-01-0125
Keywords
-
Categories
Funding
- NATIONAL CENTER FOR RESEARCH RESOURCES [M01RR012248] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R01HL028018, P01HL058512] Funding Source: NIH RePORTER
- NCRR NIH HHS [RR12248] Funding Source: Medline
- NHLBI NIH HHS [HL58512, HL28018] Funding Source: Medline
Ask authors/readers for more resources
The Ca2+-activated K+ channels of human red blood cells (RBCs) (Gardos channels, hlK1, 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 as few as 1 to 3 to as many as 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 AA and SS RBCs. In 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 through Gardos channels in each sickling episode. (C) 2005 by The American Society of Hematology.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available