Affiliations: [a] Department of Physiology, University of Oxford, Parks Road, Oxford OX1 3PT, UK | [b] Department of Haematology, Medical School, University of Birmingham, Birmingham B15 2TJ, UK
Correspondence:
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Correspondence to: Professor J. Stuart, Birmingham.
Note: [] Accepted by: Editor G.D.O. Lowe
Abstract: The KCl-cotransport pathway in the membrane of normal human red cells was activated by incubation with the SH-group reagent N-ethylmaleimide. Activation of the pathway caused progressive efflux of cell K+ over 120 min with significant loss of red cell filterability through pores of 5 µm diameter. When the pathway was activated in sickle cells, by incubation at pH 6.8 for 30 min, there was again a significant loss of filterability in excess of that caused by enhanced polymerization of sickle haemoglobin at low pH. Activation of the KCl-cotransport pathway in vivo is therefore a potentially important cause of dehydration and rheological impairment of sickle cells. Its activation in vitro is a useful new method for investigating the rheological effects of putative anti-sickling compounds, including specific inhibitors of the KCl-cotransporter.
