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© The Rockefeller University Press, 0021-9525/1999//405 $5.00
The Journal of Cell Biology, Volume 146, Number 2, , 1999 405-414

Kinetic Control of Multiple Forms of Ca²⁺ Spikes by Inositol Trisphosphate in Pancreatic Acinar Cells

^a Department of Physiology, Faculty of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Department of Physiology, Faculty of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.+81-3-5841-3325+81-3-5841-3460

hkasai{at}m.u-tokyo.ac.jp

The mechanisms of agonist-induced Ca²⁺ spikes have been investigated using a caged inositol 1,4,5-trisphosphate (IP₃) and a low-affinity Ca²⁺ indicator, BTC, in pancreatic acinar cells. Rapid photolysis of caged IP₃ was able to reproduce acetylcholine (ACh)-induced three forms of Ca²⁺ spikes: local Ca²⁺ spikes and submicromolar (<1 µM) and micromolar (1–15 µM) global Ca²⁺ spikes (Ca²⁺ waves). These observations indicate that subcellular gradients of IP₃ sensitivity underlie all forms of ACh-induced Ca²⁺ spikes, and that the amplitude and extent of Ca²⁺ spikes are determined by the concentration of IP₃. IP₃-induced local Ca²⁺ spikes exhibited similar time courses to those generated by ACh, supporting a role for Ca²⁺-induced Ca²⁺ release in local Ca²⁺ spikes. In contrast, IP₃- induced global Ca²⁺ spikes were consistently faster than those evoked with ACh at all concentrations of IP₃ and ACh, suggesting that production of IP₃ via phospholipase C was slow and limited the spread of the Ca²⁺ spikes. Indeed, gradual photolysis of caged IP₃ reproduced ACh-induced slow Ca²⁺ spikes. Thus, local and global Ca²⁺ spikes involve distinct mechanisms, and the kinetics of global Ca²⁺ spikes depends on that of IP₃ production particularly in those cells such as acinar cells where heterogeneity in IP₃ sensitivity plays critical role.

Key Words: Ca²⁺ waves • caged-IP₃ • Ca²⁺ spikes • secretion • inositol trisphosphate

© 1999 The Rockefeller University Press

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