Prolonged exposure to a K-rich medium makes the rat mast cell membrane permeable to external calcium ions

Rat mast cells, pretreated with a Ca-free, high KCl medium for more than 30 min, released histamine when subsequently exposed to a medium containing 0.1-2 mM Ca, despite the absence of voltage-dependent Ca channels. Morphological studies showed that high KCl-treated cells became swollen and that the addition of Ca caused degranulation (exocytosis). Ca-stimulated histamine release was inhibited when the high KCl treatment medium contained dinitrophenol and 2-deoxyglucose. The response to Ca was also observed when KCl in the treatment medium was replaced by RbCl, CsCl, KBr or KNO3. When the high K-treated cells were incubated with 0.5 mM 45Ca at 0-1 degree C, 45Ca uptake by these cells was much larger than that by untreated cells, suggesting that the membrane permeability to Ca of these cells is increased. Although prolonged (90 min) incubation of the cells with an isotonic KCl medium increased the rate of leakage of lactate dehydrogenase possibly reflecting extensive cell swelling, most cells recovered the ability of responding to stimulation with compound 48/80 or with simultaneous removal of Na and Ca when subsequently incubated with a Na-based medium containing Ca. Raising the KCl concentration above normal osmolarity in the treatment medium reduced the extents of cell swelling, without reducing the response to Ca addition. Under various other experimental conditions, a poor correlation was also found between the extents of swelling and the magnitude of the response to Ca. These results raised the possibility that intracellular accumulation of a particular species of anions increased membrane permeability to Ca.