Mechanisms underlying InsP(3)-evoked global Ca2+ signals in mouse pancreatic acinar cells

1. In secretory epithelial cells, complex patterns of Ca2+ signals regulate physiological processes. How these patterns are generated is still not ful ly understood. In particular, the basis of global. Ca2+ waves is not clear. 2. We have studied regional differences in InsP(3)-evoked Ca2+ release in s ingle mouse pancreatic acinar cells, using high-speed (similar to 90 frames s(-1)), high-sensitivity Ca2+ imaging combined with rapid (10 ms) spot pho tolysis (2 mu m diameter) of caged InsP(3). Within a single region we measu red Ca2+ response latency and rate of rise to construct an InsP(3) dose-res ponse relationship. 3. Spot InsP(3) liberation in the secretory pole region consistently elicit ed a dose-dependent, rapid release of Ca2+. 4. Spot InsP(3) liberation in the basal pole region of similar to 50% of ce lls elicited a similar dose-response relationship but with a lower apparent InsP(3) affinity than in the secretory pole. In the other cells, basal pol e InsP(3) liberation did not elicit active Ca2+ release, even at the highes t stimulus intensities we employed, although these same cells did respond w hen the stimulus spot was moved to different regions. 5. We conclude that in tie basal pole active sites of rapid Ca2+ release ha ve a lower functional affinity for InsP(3) than those in the secretory pole and are spread out in discrete sites across the basal pole. These properti es explain the propagation of Ca2+ waves across the basal pole that are onl y observed at higher stimulus levels.