This study reports how quantal size, or the quantity of chemical messengers within a storage granule, is regulated in platelet dense-body granules via dynamic adaption of granule size according to changing levels of granule contents. Mechanistic studies using carbon-fiber microelectrode fast-scan cyclic voltammetry and amperometry methods correlated with transmission electron microscopy analysis reveal the impact of granule structural changes on granular content secretion kinetics and highlight the dynamic interplay between soluble granule contents and membrane components in exocytosis. Despite the distinct chemical profile of platelet dense-body granules, these secretory granules act according to general biochemical/biophysical phenomena using charge-charge interactions to sequester chemical messengers and employ known conserved exocytotic machinery to deliver them; therefore, the mechanistic information obtained herein further advances the general understanding of exocytosis while revealing fundamental details about blood platelets.