Properties and regulation of human platelet cation channels.

The stimulation of calcium influx by various human platelet agonists which differ in their activation pathways was investigated. ADP activates a receptor-operated cation channel (ROC) and stimulates a phospholipase C (PLC)/inositol-trisphosphate (IP3)-mediated calcium mobilization associated with a secondary calcium influx. Thrombin only stimulates the PLC/IP3-mediated calcium mobilization and associated calcium influx, perhaps followed by an additional phase of calcium influx. The platelet calcium response after incubation with the thromboxane A2 mimetic U 46619 is similar but more transient compared to that after thrombin stimulation. Tert-butylhydroquinone (an inhibitor of endoplasmatic reticulum Ca(2+)-ATPases and cyclooxygenase) elevates cytosolic calcium levels by emptying intracellular calcium stores and stimulates a biphasic calcium influx. Activation of platelet cAMP- and cGMP-dependent protein kinases inhibits the ADP- and thrombin-evoked, calcium store-associated cation influx, but not the fast receptor operated cation influx induced by ADP. Experiments with various ADP-analogs, ATP and ATP-gamma-S suggest that two different ADP-receptors may mediate the calcium responses in human platelets.