Bepridil protects sickle cells against the adverse rheological effects of cyclical deoxygenation.
Calcium influx into sickle cells, with consequential activation of the Ca2(+)-activated K+ efflux (Gardos) channel, is a potential cause of cellular dehydration and loss of deformability. Bepridil, a recently described inhibitor of the Gardos channel, was found at pharmacological concentration (1 mumol/l) to inhibit significantly (P less than 0.01) the loss of deformability when sickle cells were subjected to cycles of oxygenation-deoxygenation for 15 h at 37 degrees C. Bepridil also inhibited significantly (P less than 0.005) the formation of irreversibly sickled cells. Drugs that preserve the K+ and therefore water content of erythrocytes are of potential value for hydrotherapy of sickle cell disease.
Johnston
M N
MN
Department of Haematology, Medical School, University of Birmingham.
Ellory
J C
JC
Stuart
J
J
D000755:Anemia, Sickle Cell / Q000097:blood*; D015764:Bepridil / Q000494:pharmacology*; D004907:Erythrocyte Deformability / Q000187:drug effects*; D004913:Erythrocytes, Abnormal / Q000187:drug effects*; D006801:Humans; D010100:Oxygen / Q000097:blood*
D015764:Bepridil; D010100:Oxygen