Effects of the lonophore A23187 on the blood platelets II. Influence on ultrastructure

A23187, an ionophore which selectively transports calcium across cell membranes into cytoplasm or releases the divalent cation from intracellular storage sites, was shown in previous studies to stimulate platelet aggregation and the release reaction. The nature of its influence on platelet function suggested that an increase in cytoplasmic calcium ion concentration might be a critical factor linking stimulation to secretion through the platelet contractile mechanism. The present investigation has examined the effects of A23187 in platelet ultrastructure and aggregation after incubation with various concentrations of the drug. Scanning and transmission electron microscopy revealed changes in the form and internal organization of platelets following exposure to A23187 that were identical to those which develop in the cells after exposure to potent agents such as collagen and thrombin. High concentrations of ionophore caused destruction of the platelets on prolonged incubation, while the effects of low concentrations on structure and aggregation reversed completely. Recovered platelets were as sensitive to other aggregating agents as control cells. The findings support the concept that platelets are a form of muscle cell and the internal transformation stimulated by A23187 and other aggregating agents is a manifestation of contractile activity. Inactivation of A23187 by plasma followed by recovery of unaltered appearance indicates that platelets have an active mechanism for reducing the level of cytoplasmic calcium.