Non-electrolyte permeability of deoxygenated sickle cells compared

Abstract

The passive permeability pathways of red cells are poorly defined, with the exception of the Gardos channel. Several cation and anion pathways can be induced by a variety of manoeuvres, however, including treatment with oxidants, low ionic strength (LIS), shrinkage, swelling and also infection with the intra-erythrocytic malaria parasite. Several of these stimuli (malaria, swelling, LIS), in addition, also activate a non-electrolyte this permeability. Sickle cells uniquely show a deoxygenation-induced pathway, which is termed P(sickle) and is usually considered to be a conductive cationic pathway. In this report, we explore further the extent to which this permeability pathway of deoxygenated sickle cells is available for non-electrolyte transport. We show that a number of solutes are permeable, with greater permeability to sugars (notably lactose and maltose) and smaller molecules, and less to charged or zwitterionic species. Red cells from heterozygous HbSC patients also showed deoxygenation-induced haemolysis in isosmotic sucrose solution, though to a slightly lesser extent than for red cells from homozygous sickle cell patients. In contrast to sickle cells, red cells from beta-thalassaemic patients did not show haemolysis in isosmotic sucrose solutions, regardless of the O(2) tension. Of the secondary cellular changes resulting from incubation in non-electrolyte solutions (which include imposition of a highly positive membrane potential, marked intracellular alkalinisation and cell shrinkage), none appear to correlate with activation of the non-electrolyte permeability. Rather, findings indicate that it is low ionic strength per se that is responsible. Normal red cells also show changes in ionic and non-electrolyte permeability in low ionic strength media, and these permeabilities are compared to those found in deoxygenated sickle cells. The extent to which these different permeabilities in normal and sickle red cells can be ascribed to one or more common pathways remains to be determined.