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

Correspondence to: Haruo Kasai, Department of Physiology, Faculty of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan., hkasai{at}m.u-tokyo.ac.jp (E-mail), +81-3-5841-3460 (phone), +81-3-5841-3325 (fax)

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

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Shah, A. U., Grant, W. M., Latif, S. U., Mannan, Z. M., Park, A. J., Husain, S. Z. (2008). Cyclic AMP accelerates calcium waves in pancreatic acinar cells. Am. J. Physiol. Gastrointest. Liver Physiol. 294: G1328-G1334 [Abstract] [Full Text]  
• Hatakeyama, H., Kishimoto, T., Nemoto, T., Kasai, H., Takahashi, N. (2006). Rapid glucose sensing by protein kinase A for insulin exocytosis in mouse pancreatic islets. J. Physiol. 570: 271-282 [Abstract] [Full Text]  
• Leite, M. F., Thrower, E. C., Echevarria, W., Koulen, P., Hirata, K., Bennett, A. M., Ehrlich, B. E., Nathanson, M. H. (2003). Nuclear and cytosolic calcium are regulated independently. Proc. Natl. Acad. Sci. USA 100: 2975-2980 [Abstract] [Full Text]  
• Song, J. C., Rangachari, P. K., Matthews, J. B. (2002). Opposing effects of PKCalpha and PKCepsilon on basolateral membrane dynamics in intestinal epithelia. Am. J. Physiol. Cell Physiol. 283: C1548-C1556 [Abstract] [Full Text]  
• Dumollard, R., Carroll, J., Dupont, G., Sardet, C. (2002). Calcium wave pacemakers in eggs. J. Cell Sci. 115: 3557-3564 [Abstract] [Full Text]  
• Ashby, M. C., Tepikin, A. V. (2002). Polarized Calcium and Calmodulin Signaling in Secretory Epithelia. Physiol. Rev. 82: 701-734 [Abstract] [Full Text]  
• Shin, D. M., Luo, X., Wilkie, T. M., Miller, L. J., Peck, A. B., Humphreys-Beher, M. G., Muallem, S. (2001). Polarized Expression of G Protein-coupled Receptors and an All-or-None Discharge of Ca2+ Pools at Initiation Sites of [Ca2+]i Waves in Polarized Exocrine Cells. J. Biol. Chem. 276: 44146-44156 [Abstract] [Full Text]  
• Dumollard, R., Sardet, C. (2001). Three different calcium wave pacemakers in ascidian eggs. J. Cell Sci. 114: 2471-2481 [Abstract] [Full Text]  
• Giovannucci, D. R., Bruce, J. I. E., Straub, S. V., Arreola, J., Sneyd, J., Shuttleworth, T. J., Yule, D. I. (2002). Cytosolic Ca2+ and Ca2+-activated Cl- current dynamics: insights from two functionally distinct mouse exocrine cells. J. Physiol. 540: 469-484 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents