A low cation conductance and a high anion conductance are characteristic of
normal erythrocytes, In sickle cell anemia, the polymerization of hemoglob
in S (HbS) under conditions of low oxygen tension is preceded by an increas
e in cation conductance. This increase in conductance is mediated in part t
hrough Ca+ +-activated K+ channels, A net efflux of potassium chloride (KCI
) leads to a decrease in intracellular volume, which in turn increases the
rate of HbS polymerization, Treatments minimizing the passive transport of
ions and solvent to prevent such volume depletion might include inhibitors
targeting either the Ca+ +-activated K+ channel or the anion conductance, N
S1652 is an anion conductance inhibitor that has recently been developed. I
n vitro application of this compound lowers the net KCI loss from deoxygena
ted sickle cells from about 12 mmol/L cells/h to about 4 mmol/L cells/h, a
value similar to that observed in oxygenated cells. Experiments performed i
n mice demonstrate that NS1652 is well tolerated and decreases red cell ani
on conductance in vivo. (C) 2000 by The American Society of Hematology.