Cellular stress activates a non-selective Ca2+-permeable cation conductance in human erythrocytes. The entry of Ca2+ leads to activation of K+ channels and subsequent erythrocyte shrinkage, and to stimulation of a scramblase with subsequent exposure of phosphatidylserine at the cell surface. In the present study, we explored whether erythrocyte shrinkage and phosphatidylserine exposure might be influenced by cytoskeleton-targeting drugs, i.

e. colchicine and some synthetic colchicine analogs. Removal of Cl- enhanced annexin binding and decreased forward scatter, effects significantly inhibited by colchicine. Furthermore, colchicine also blunted spontaneous eryptosis, i. e. shrinkage and phosphatidyl-serine exposure of non-stressed cells. To investigate the structural basis of the colchicine effect, colchicine analogs were synthesized and their effect was tested in vitro. The results revealed that the nitrogen bound to the natural colchicine carbon ring structure is necessary for its inhibitory effect. In conclusion, several colchicine analogs blunt spontaneous as well as the Cl-removal-activated phosphatidylserine exposure of erythrocytes, presumably by interfering with the cytoskeletal organisation of this specialized cell type.