Lithium-induced suicidal erythrocyte death

Abstract

Lithium (Li⁺), an effective drug for treatment of bipolar disorders, is known to alter several Ca²⁺ transporting systems. Increased cellular Ca²⁺ has in turn been shown to stimulate eryptosis, the suicidal death of erythrocytes. Eryptosis is characterised by exposure of phosphatidylserine (PS) at the erythrocyte surface and by cell shrinkage. The present experiments explored whether Li⁺ influences eryptosis. In erythrocytes from healthy volunteers, cytosolic Ca²⁺ activity (Fluo-3 fluorescence), cell volume (forward scatter) and PS exposure (annexin V binding) were determined by fluorescence-activated cell sorting analysis. Exposure to Li⁺ (≥1 mM) did not significantly modify forward scatter but significantly increased cytosolic Ca²⁺ activity (within 3 h) and annexin binding (within 48 h). The effect was paralleled by increase of cellular adenosine triphosphate concentration. Glucose depletion (24 h) strongly increased PS exposure, an effect significantly enhanced in the presence of Li⁺ (≥1 mM). In conclusion, Li⁺ triggers suicidal erythrocyte death, an effect at least partially due to increase of cytosolic Ca²⁺ activity.