The Journal of General Physiology
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Published online April 30, 2007
doi:10.1085/jgp.200709766
The Journal of General Physiology, Vol. 129, No. 5, 429-436
The Rockefeller University Press, 0022-1295 $30.00
© 2007 Tiffert et al.
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ARTICLE

 Age Decline in the Activity of the Ca2+-sensitive K+ Channel of Human Red Blood Cells



Teresa Tiffert1, Nuala Daw1, Zipora Etzion2, Robert M. Bookchin2, and Virgilio L. Lew1

1 Department of Physiology, Development and Neuroscience, University of Cambridge, Downing Street, Cambridge CB2 3EG, UK
2 Department of Medicine, Albert Einstein College of Medicine, Bronx, NY 10461

Correspondence to Teresa Tiffert: jtt1000{at}cam.ac.uk

The Ca2+-sensitive K+ channel of human red blood cells (RBCs) (Gardos channel, hIK1, hSK4) was implicated in the progressive densification of RBCs during normal senescence and in the mechanism of sickle cell dehydration. Saturating RBC Ca2+ loads were shown before to induce rapid and homogeneous dehydration, suggesting that Gardos channel capacity was uniform among the RBCs, regardless of age. Using glycated hemoglobin as a reliable RBC age marker, we investigated the age–activity relation of Gardos channels by measuring the mean age of RBC subpopulations exceeding a set high density boundary during dehydration. When K+ permeabilization was induced with valinomycin, the oldest and densest cells, which started nearest to the set density boundary, crossed it first, reflecting conservation of the normal age–density distribution pattern during dehydration. However, when Ca2+ loads were used to induce maximal K+ fluxes via Gardos channels in all RBCs (Fmax), the youngest RBCs passed the boundary first, ahead of the older RBCs, indicating that Gardos channel Fmax was highest in those young RBCs, and that the previously observed appearance of uniform dehydration concealed a substantial degree of age scrambling during the dehydration process. Further analysis of the Gardos channel age–activity relation revealed a monotonic decline in Fmax with cell age, with a broad quasi-Gaussian Fmax distribution among the RBCs.

Abbreviations used in this paper: DEP, diethylphthalate; Hb A1c, glycated hemoglobin; Hct, hematocrit; RBC, human red blood cell.


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