Deoxygenation permeabilizes sickle cell anaemia red cells to magnesium and reverses its gradient in the dense cells.

Abstract

SUMMARY1. Our findings of a low total magnesium content in the dense fraction (over 1418 g ml-1) of sickle cell anaemia (SS) red cells seemed inconsistent with the low Mg2+ permeability and outward Mg2+ gradient seen in normal red cells, and prompted studies of the Mg2+ permeability and equilibria in the SS cells.2 5. The above findings suggested that the documented low sodium pump fluxes in dense SS cells may result from an increased Mg2+:ATP ratio, which is known to inhibit Na+-K+ exchange fluxes through the sodium pump. If so, deoxygenation, by increasing the Mg2+: ATP ratio, should inhibit the pump further, whereas increasing ATP should relieve the inhibition. Experiments designed to test this possibility showed that in these dense SS cells, the ouabain-sensitive K(86Rb) influx was low in oxygenated cells, was reduced further by deoxygenation, but was substantially increased after treatment with inosine, pyruvate and phosphate to increase their organic phosphate pool. These results were thus consistent with such a mechanism for Na+ pump inhibition in the dense SS cells.

Do HbSS erythrocytes lose KCl in physiological conditions?

“…4, plasma was carefully gassed with a 95% O 2 and 5% CO 2 mixture, and the pH titrated at 37ЊC. Since variation of pO 2 modifies KCl cotransport activity in sickle cells (Canessa et al, 1987;Ortiz et al, 1990), the cells were also fully oxygenated during the K + influx measurement. Finally, variation in K + concentration as well as in osmolarity represent factors which will affect measured KCl cotransport activity (Brugnara et al, 1986;Brugnara & Tosteson, 1987), and these two parameters have been adjusted to the same values in all solutions.…”

Effects of deoxygenation on active and passive Ca2+ transport and cytoplasmic Ca2+ buffering in normal human red cells.

“…Therefore, the observed reduction cannot be attributed to pH. It is well documented that deoxygenation causes significant changes in [Mg2"], and [Mg2`]j/[ATP]1 (Berger, Janig, Gerber, Ruckpaul & Rapoport, 1973;Flatman, 1980;, which, in turn, can influence the Na+-K+-ATPase and Ca2+-Mg2+-ATPase as well as the active and passive ion transport functions of the red cell membrane b; Flatman & Lew, 1981;Flatman, 1988;Ortiz, Lew & Bookchin, 1990 (Lew et al 1982 We wish to thank the Wellcome Trust (UK) and the NIH (USA, Grants HL28018 and HL21016) for funds, Dr J. E. Raftos for helpful comments, and Mrs A. Gray for excellent technical assistance.…”

Dipyridamole inhibits sickling-induced cation fluxes in sickle red blood cells

“…[2][3][4][5][6] This sicklinginduced change in permeability leads to cation loss and dehydration by 3 potential mechanisms: (1) imbalance between K ϩ loss and Na ϩ gain via the sickling-induced pathway per se in the presence of external Ca ϩϩ , 3,4 (2) unbalanced compensation by the Na ϩ pump (3 Na out for 2 K in ) in response to elevated cellular Na ϩ , 9 (3) increased Ca ϩϩ influx, with transient elevation of cellular Ca ϩϩ leading to activation of the Ca ϩϩ -dependent K ϩ channel. 4,8,10 In turn, the resultant cellular dehydration potentiates sickling because of the high dependence of the rate of polymerization on HbS concentration, 12 producing a vicious cycle of sickling 3 dehydration 3 sickling.…”