Two pathways for store-mediated calcium entry in human platelets

In human platelets and other non-excitable cell types depletion of the intracellular calcium stores promotes calcium entry across the plasma membrane. Although the mechanism of this store-mediated calcium entry remains uncertain, it has been suggested that a tyrosine phosphorylation step could be involved. In support of this hypothesis various tyrosine kinase inhibitors have been shown to reduce store-mediated calcium entry in platelets, although this inhibition is never complete. Here we investigate the properties of store-mediated calcium entry in human platelets during the time course of its activation. Our data suggest that at least two pathways may contribute to store-mediated calcium entry in these cells. An early component, activated soon after the initiation of Ca2+ store depletion, is insensitive to trivalent cations, SKF 96365 and tyrosine kinase inhibitors. This is followed by a second component which is inhibited by La3+, SKF 96365 and by tyrosine kinase inhibitors. These results suggest a role for tyrosine kinases in generating only the later stages of store-mediated calcium entry in platelets and may explain the incomplete inhibition of this pathway by inhibitors of tyrosine kinases.