Although Ca²⁺ plays a critical function in relaying intracellular messages, the role of subcellular organelles in the dynamics of intracellular Ca²⁺ still remains largely unexplored. We recently demonstrated that secretory granules can signal their own export from the cell by releasing Ca²⁺ to the cytosol. Oscillations and release of Ca²⁺ in/from the granule result from the combined action of a Ca²⁺/K⁺ ion exchange process that occurs in the granule's matrix, and the sequential activation of two Ca²⁺‐sensitive ion channels: an inositol 1,4,5‐trisphosphate receptor Ca²⁺ channel (InsP₃R) and an apamin‐sensitive Ca²⁺‐activated K⁺ channel (ASK_Ca). The results reported here from studies using isolated mucin granules indicate that intralumenal granular Ca²⁺ oscillations ([Ca²⁺]_L) and the corresponding cyclical release of Ca²⁺ to the cytosol induced by InsP₃ are accompanied by corresponding intragranular pH_G oscillations. Our data show that K⁺‐induced unbinding of Ca²⁺ from the mucin matrix increases as the pH_G declines. These observations suggest that oscillations of pH_G can modulate the gain of the Ca²⁺/K⁺ ion exchange process, thereby controlling the amplitude of [Ca²⁺]_L oscillations and the granule‐cytosol release gradient of [Ca²⁺].