Sickle red cell dehydration: mechanisms and interventions

A critical link between the single molecular defect in sickle cell anemia and the extensive pathology of this disease is the reversible increase in red cell membrane permeability generated by hemoglobin S polymers in the deoxygenated state. This permeability, usually described as triggers a chain of events in which two constitutive transporters of the red cell membrane become activated-the recently cloned intermediate conductance, Ca2+-sensitive K channel, and the electroneutral K:Cl cotransporter-lead in g to sickle cell dehydration. This article reviews knowledge of the dehydration mechanism, stressing the marked heterogeneity of dehydration rates in sickle cell populations, and discusses recent contributions to understanding of the function and regulation of P-sickle, Ca2+-sensitive K channel, and K:Cl cotransporter, and of therapies targeted at these transporters. Curr Opin Hematol 2002,9:107-110 (C)2002 Lippincott Williams Wilkins, Inc.