Monensin augments capacitative Ca2+ entry and subsequent aggregation of platelets via an intracellular alkalosis-mediated mechanism

Effects of monensin, an ionophore that facilitates the transmembrane exchange of Na+ for H+, on capacitative Ca2+ entry (CCE) of platelets were investigated. CCE of human platelets was induced by addition of Ca2+ to a nominally Ca2+-free medium after release of intracellular stored Ca2+ caused by thapsigargin. CCE was strongly inhibited by SKF-96365 (1-[β-(3-[4-methoxyphenyl]propoxy)-4-methoxyphenethyl]-1H-imidazole hydrochloride). Monensin significantly increased SKF-96365-sensitive CCE and subsequent platelet aggregation. Monensin also induced a sustained increase in intracellular pH. The augmenting effect of monensin on CCE and subsequent platelet aggregation was not observed in the presence of sodium propionate, which canceled intracellular alkalinization induced by monensin. These results suggest that monensin augments CCE of platelets by a mechanism mediated by intracellular alkalosis.