Distribution of dehydration rates generated by maximal Gardos-channel activation in normal and sickle red blood cells.

Blood
V L LewR M Bookchin

Abstract

The Ca(2+)-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 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 Ca(2+)-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 channel...Continue Reading

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Citations

Sep 22, 2010·Pflügers Archiv : European journal of physiology·Michael FöllerStephan M Huber
May 2, 2007·The Journal of General Physiology·Teresa TiffertVirgilio L Lew
Dec 3, 2014·Toxicology and Applied Pharmacology·Itzel-Citlalli Aguilar-DoradoJosé-Víctor Calderón-Salinas
May 7, 2009·Pain Medicine : the Official Journal of the American Academy of Pain Medicine·Pasquale NiscolaPaolo Cianciulli
Jan 21, 2012·Blood Cells, Molecules & Diseases·Qiuying ChenRhoda Elison Hirsch
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Jun 7, 2008·Bioelectrochemistry·Maria Baunbaek, Poul Bennekou
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Jul 17, 2015·American Journal of Hematology·Natasha ArcherCarlo Brugnara
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Feb 15, 2013·American Journal of Physiology. Cell Physiology·Colin J StonekingMichael J Mason

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