In red cells from normal individuals (HbA cells), the K + -Cl - cotransporter (KCC) is inactivated by low O 2 tension whilst in those from sickle cell patients (HbS cells), it remains fully active. Changes in free intracellular [Mg 2+ ] have been proposed as a mechanism. In HbA cells, KCC activity was stimulated by Mg 2+ depletion and inhibited by Mg 2+ loading but the effect of O 2 was independent of Mg 2+ . At all [Mg 2+ ] i s, the transporter was stimulated in oxygenated cells, minimally active in deoxygenated ones. By contrast, the stimulatory effects of O 2 was abolished by inhibitors of protein (de)phosphorylation. HbS cells had elevated KCC activity, which was of similar magnitude in oxygenated and deoxygenated cells, regardless of Mg 2+ clamping. In deoxygenated cells, the antisickling agent dimethyl adipimidate inhibited sickling, P sickle and KCC. Results indicate a role for protein phosphorylation in O 2 dependence of KCC, with different activities of the relevant enzymes in HbA and HbS cells, probably dependent on Hb polymerisation, but not on [Mg 2+ ] i .
- KCI cotransport
- Sickle cell