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.
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26 July 1999
Article|
July 26 1999
Kinetic Control of Multiple Forms of Ca2+ Spikes by Inositol Trisphosphate in Pancreatic Acinar Cells
Koichi Ito,
Koichi Ito
aDepartment of Physiology, Faculty of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
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Yasushi Miyashita,
Yasushi Miyashita
aDepartment of Physiology, Faculty of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
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Haruo Kasai
Haruo Kasai
aDepartment of Physiology, Faculty of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
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Koichi Ito
aDepartment of Physiology, Faculty of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Yasushi Miyashita
aDepartment of Physiology, Faculty of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
Haruo Kasai
aDepartment of Physiology, Faculty of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan
1.used in this paper: ACh, acetylcholine; BTC, benzothiazole coumarin; [Ca2+]i, cytosolic Ca2+ concentration; CICR, Ca2+-induced Ca2+ release; IP3, inositol 1,4,5-trisphosphate; PLC, phospholipase C
Received:
March 29 1999
Revision Requested:
June 10 1999
Accepted:
June 15 1999
Online ISSN: 1540-8140
Print ISSN: 0021-9525
© 1999 The Rockefeller University Press
1999
The Rockefeller University Press
J Cell Biol (1999) 146 (2): 405–414.
Article history
Received:
March 29 1999
Revision Requested:
June 10 1999
Accepted:
June 15 1999
Citation
Koichi Ito, Yasushi Miyashita, Haruo Kasai; Kinetic Control of Multiple Forms of Ca2+ Spikes by Inositol Trisphosphate in Pancreatic Acinar Cells. J Cell Biol 26 July 1999; 146 (2): 405–414. doi: https://doi.org/10.1083/jcb.146.2.405
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