Rheological effect of activation of the KCl-cotransport pathway in normal and sickle erythrocytes

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.