Mouse mast cell secretory granules can function as intracellular ionic oscillators

Fluorescent Ca2+ probes and digital photo-sectioning techniques were used t o directly study the dynamics of Ca2+ in isolated mast cell granules of nor mal (CB/J) and beige (Bg(i)/Bg(i)) mice. The resting intraluminal free Ca2 concentration ([Ca2+](L)) is 25 +/- 4.2 muM (mean +/- SD, n = 68). Exposur e to 3 muM inositol 1,4,5-trisphosphate (InsP(3)) induced periodic oscillat ions of luminal Ca2+ ([Ca2+](L)) of similar to 10 muM amplitude and a perio d around 8-10 s. The [Ca2+](L) oscillations were accompanied by a correspon ding oscillatory release of [Ca2+](L) to the extraluminal space. Control ex periments using ruthenium red (2 muM) and thapsigargin (100 nM) ruled out a rtifacts derived from the eventual presence of mitochondria or endoplasmic reticulum in the isolated granule preparation. Oscillations of [Ca2+](L) an d Ca2+ release result from a Ca2+/K+ exchange process whereby bound Ca is d isplaced from the heparin polyanionic matrix by inflow of K+ into the granu lar lumen via an apamin-sensitive Ca2+-sensitive K+ channel (ASK(Ca)), wher eas Ca2+ release takes place via an InsP(3)-receptor-Ca2+ (InsP(3)-R) chann el. These results are consistent with previous observations of [Ca2+](L) os cillations and release in/from the endoplasmic reticulum and mucin granules , and suggest that a highly conserved common mechanism might be responsible for [Ca2+](L) oscillations and quantal periodic Ca2+ release in/from intra cellular Ca2+ storage compartments.