Release of α and δ-granule contents of platelets in RanBP10^−/− mice. (A) Similar mepacrine uptake in platelets of either genotype (MFI = mean fluorescence intensity (left panel). Mepacrine release after 5 minutes is overall unaltered between wild-type and RanBP10-null platelets, whereas it is slightly slower in mutant platelets after 1 minute when suboptimal thrombin concentrations (0.1 or 0.2 U/mL) are used. Data show an average of 6 independent experiments. Error bars depict the standard deviation. (B) Maximal ATP release in whole blood of RanBP10-null animals and controls was determined by aggregoluminometry revealing a slightly increased ATP release after treatment with 0.2, 0.4, or 1 U/mL thrombin or with 2 or 5 μg/mL collagen. (C) Serotonin release in response to 0.5μM PAR4p treatment showed no difference after 1, 3, or 5 minutes between wild-type and mutant platelets. (D) α and dense granules were counted on electron micrographs showing no difference in intact platelets. (E) Measurements of the diameter of α and dense-granules show that there is no difference between wild-type and RanBP10-null platelets. (F) Wild-type and RanBP10-null platelets were activated with 5 μg/mL collagen in the presence or absence of 0.25μM ADP. This concentration had little impact on collagen-induced aggregation in wild-type platelets (black), but restored attenuated shape change and aggregation in knockout platelets (gray curves) almost to wild-type levels (left panel). Time of shape change is significantly prolonged in mutant animals, but can be restored in the presence of threshold ADP concentrations (right panel). Mean of 5 experiments is shown, error bars indicate standard deviation (*P < .05).