Trisphosphate in Pancreatic Acinar Cells

The mechanisms of agonist-induced Ca 2 1 spikes have been investigated using a caged inositol 1,4,5-trisphosphate (IP 3 ) and a low-affinity Ca 2 1 indicator, BTC, in pancreatic acinar cells. Rapid photolysis of caged IP 3 was able to reproduce acetylcholine (ACh)induced three forms of Ca 2 1 spikes: local Ca 2 1 spikes and submicromolar ( , 1 m M) and micromolar (1–15 m M) global Ca 2 1 spikes (Ca 2 1 waves). These observations indicate that subcellular gradients of IP 3 sensitivity underlie all forms of ACh-induced Ca 2 1 spikes, and that the amplitude and extent of Ca 2 1 spikes are determined by the concentration of IP 3 . IP 3 -induced local Ca 2 1 spikes exhibited similar time courses to those generated by ACh, supporting a role for Ca 2 1 -induced Ca 2 1 release in local Ca 2 1 spikes. In contrast, IP 3 induced global Ca 2 1 spikes were consistently faster than those evoked with ACh at all concentrations of IP 3 and ACh, suggesting that production of IP 3 via phospholipase C was slow and limited the spread of the Ca 2 1 spikes. Indeed, gradual photolysis of caged IP 3 reproduced ACh-induced slow Ca 2 1 spikes. Thus, local and global Ca 2 1 spikes involve distinct mechanisms, and the kinetics of global Ca 2 1 spikes depends on that of IP 3 production particularly in those cells such as acinar cells where heterogeneity in IP 3 sensitivity plays critical role.