Platelet dense-granule centralization and the persistence of ADP secretion

After activation of a human platelet, its adenosine diphosphate (ADP)-containing dense granules are moved toward the platelet's center and release their ADP into the channels of the open canalicular system (OCS). Mathematical modeling is used to investigate a possible role of this centralization in prolonging the duration of ADP secretion compared with direct release at the platelet's plasma membrane. A key parameter is the degree to which the diffusion of ADP through the narrow and tortuous channels of the OCS is slower than ADP diffusion in plasma. For small but physiologically plausible values of this parameter and with use of literature-based values for the amount and concentration of dense-granule ADP, the platelet serves as a continuing source of ADP; the concentration of ADP in the immediate environment of the platelet remains high enough to activate nearby platelets for 5-13 s, many times longer than if ADP were released directly at the plasma membrane.