Regulation of release from isolated adrenergic secretory vesicles by ATP-mediated changes in transmembrane potential...

Isolated chromaffin granules release their contents when exposed to calcium, magnesium, ATP, and high levels of chloride ions. The mechanism of release is not well-understood, but changes in anion permeability may be involved. We found that another anion, thiocyanate (SCN-), also activated release in a fashion similar to chloride, while isethionate (HO-CH2-CH2SO3-) an impermeant anion, was inactive. Mg++-ATP was found to activate the uptake of 36Cl and 14C-SCN, leading us to conclude that activation of anion uptake might be involved in the release process. The 36Cl and the 14C-SCN compartments were then compared by studying displacement of the trace anions by excess cold mass. Chloride and SCN displaced large amounts of both 36Cl and 14C-SCN, while isethionate displaced little of either tracer anion. We suggest, on the basis of these data, that ATP-mediated anion uptake may be the basis for the release mechanism. Release may occur as a consequence of anion and subsequent water uptake into granules, resulting in osmotic imbalance and osmotic shock. This may also be of physiologic importance, and we propose a cellular model for secretion based on the biochemical properties of the isolated chromaffin granule.