Studies in model systems, as well as observations in intact cells, suggest that osmotic swelling of secretory granules is an essential step in exocytosis. A model is proposed whereby the low pH recorded in most secretory organelles could provide the driving force for granule swelling. The model assumes that during stimulation an exchange of H+ for alkali cations is triggered across the granule membrane. The outgoing H+ are rapidly replaced by the internal buffering capacity with a concomitant osmotic gain. The exchange is independent of anions and could be triggered by cytoplasmic Ca2+. The H+-pump is responsible for the ΔpH but independent of the exchange mechanism.
