Rat mast cells permeabilized with ATP secrete histamine in response to calcium ions buffered in the micromolar range.

1. Rat mast cells with ATP (0.5-4 micro M) in the absence of divalent cations (so that almost all the ATP is present as ATP4-) became permeable to normally impermeant aqueous solutes, added extracellularly. These include the stable complexes Co HEDTA and Ca EDTA, and 6-carboxyfluorescein but not inulin. At 4 micro M-ATP4- the space accessible to Ca EDTA is 89% of that occupied by 3H2O. 2. The kinetics of solute entry are regulated by the concentration of ATP4-. 3. Ca2+, buffered in the range 1-10 micro M with HEDTA, causes histamine secretion from mast cells that have been rendered permeable with ATP4-. The extent of secretion increases as the concentration of ATP4- is raised from 3 to 5 micro M. With extracellular Ca2+ present as physiological (millimolar) concentrations, the effect of increasing ATP4- through this range is to inhibit secretion. 4. The rates of histamine secretion and of 32P-metabolite leakage from 32P-prelabelled cells in the presence of micromolar concentrations of Ca2+, were compared. The kinetics of both processes are regulated by the concentration of ATP4-, but not Ca2+.