A biophysical model of the chromaffin granule. Accurate description of the kinetics of ATP and Cl- dependent granule lysis

A model is constructed to describe the behavior of isolated chromaffin granules (secretory vesicles of the adrenal medulla) when they are induced to release their contents by incubation with MgATP and Cl-. The model is based on the assumption that the release event is osmotic lysis due to the ATPase dependent influx of protons and osmotically active Cl- ions. The consequences of this influx of osmotically active particles are predicted from osmotic fragility curves determined by suspending granules in hypotonic media. Turbidity measurements on granule suspensions undergoing the ATP and Cl- dependent release reaction are used to fit the parameters of the model. The model then successfully described the time course, Cl- dependence, ATP dependence, and osmotic strength suppression of the release event as monitored either by measurement of turbidity changes or of epinephrine release. The degree of suppression of release predicted in hypertonic media is also in agreement with published data on hypertonic suppression of exocytosis from several cell types: chromaffin cells, blood platelets, and parathyroid cells. Therefore, the model may also provide an accurate description of some of the events occurring during exocytosis.