Skip to main content
NCBI home page
Biophysical Journal logoLink to Biophysical Journal
. 2000 May;78(5):2298–2306. doi: 10.1016/S0006-3495(00)76776-2

A bimodal pattern of InsP(3)-evoked elementary Ca(2+) signals in pancreatic acinar cells.

K E Fogarty 1, J F Kidd 1, R A Tuft 1, P Thorn 1
PMCID: PMC1300821  PMID: 10777728

Abstract

InsP(3)-evoked elementary Ca(2+) release events have been postulated to play a role in providing the building blocks of larger Ca(2+) signals. In pancreatic acinar cells, low concentrations of acetylcholine or the injection of low concentrations of InsP(3) elicit a train of spatially localized Ca(2+) spikes. In this study we have quantified these responses and compared the Ca(2+) signals to the elementary events shown in Xenopus oocytes. The results demonstrate, at the same concentrations of InsP(3), Ca(2+) signals consisting of one population of small transient Ca(2+) release events and a second distinct population of larger Ca(2+) spikes. The signal mass amplitudes of both types of events are within the range of amplitudes for the elementary events in Xenopus oocytes. However, the bimodal Ca(2+) distribution of Ca(2+) responses we observe is not consistent with the continuum of event sizes seen in Xenopus. We conclude that the two types of InsP(3)-dependent events in acinar cells are both elementary Ca(2+) signals, which are independent of one another. Our data indicate a complexity to the organization of the Ca(2+) release apparatus in acinar cells, which might result from the presence of multiple InsP(3) receptor isoforms, and is likely to be important in the physiology of these cells.

Full Text

The Full Text of this article is available as a PDF (378.8 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adkins C. E., Taylor C. W. Lateral inhibition of inositol 1,4,5-trisphosphate receptors by cytosolic Ca(2+). Curr Biol. 1999 Oct 7;9(19):1115–1118. doi: 10.1016/s0960-9822(99)80481-3. [DOI] [PubMed] [Google Scholar]
  2. Berridge M. J. Elementary and global aspects of calcium signalling. J Physiol. 1997 Mar 1;499(Pt 2):291–306. doi: 10.1113/jphysiol.1997.sp021927. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bootman M. D., Berridge M. J., Lipp P. Cooking with calcium: the recipes for composing global signals from elementary events. Cell. 1997 Oct 31;91(3):367–373. doi: 10.1016/s0092-8674(00)80420-1. [DOI] [PubMed] [Google Scholar]
  4. Bootman M., Niggli E., Berridge M., Lipp P. Imaging the hierarchical Ca2+ signalling system in HeLa cells. J Physiol. 1997 Mar 1;499(Pt 2):307–314. doi: 10.1113/jphysiol.1997.sp021928. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. De Koninck P., Schulman H. Sensitivity of CaM kinase II to the frequency of Ca2+ oscillations. Science. 1998 Jan 9;279(5348):227–230. doi: 10.1126/science.279.5348.227. [DOI] [PubMed] [Google Scholar]
  6. De Smedt H., Missiaen L., Parys J. B., Henning R. H., Sienaert I., Vanlingen S., Gijsens A., Himpens B., Casteels R. Isoform diversity of the inositol trisphosphate receptor in cell types of mouse origin. Biochem J. 1997 Mar 1;322(Pt 2):575–583. doi: 10.1042/bj3220575. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Deisseroth K., Heist E. K., Tsien R. W. Translocation of calmodulin to the nucleus supports CREB phosphorylation in hippocampal neurons. Nature. 1998 Mar 12;392(6672):198–202. doi: 10.1038/32448. [DOI] [PubMed] [Google Scholar]
  8. Dolmetsch R. E., Xu K., Lewis R. S. Calcium oscillations increase the efficiency and specificity of gene expression. Nature. 1998 Apr 30;392(6679):933–936. doi: 10.1038/31960. [DOI] [PubMed] [Google Scholar]
  9. Hagar R. E., Burgstahler A. D., Nathanson M. H., Ehrlich B. E. Type III InsP3 receptor channel stays open in the presence of increased calcium. Nature. 1998 Nov 5;396(6706):81–84. doi: 10.1038/23954. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
  11. Ito K., Miyashita Y., Kasai H. Kinetic control of multiple forms of Ca(2+) spikes by inositol trisphosphate in pancreatic acinar cells. J Cell Biol. 1999 Jul 26;146(2):405–413. doi: 10.1083/jcb.146.2.405. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Ito K., Miyashita Y., Kasai H. Micromolar and submicromolar Ca2+ spikes regulating distinct cellular functions in pancreatic acinar cells. EMBO J. 1997 Jan 15;16(2):242–251. doi: 10.1093/emboj/16.2.242. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Kasai H., Li Y. X., Miyashita Y. Subcellular distribution of Ca2+ release channels underlying Ca2+ waves and oscillations in exocrine pancreas. Cell. 1993 Aug 27;74(4):669–677. doi: 10.1016/0092-8674(93)90514-q. [DOI] [PubMed] [Google Scholar]
  14. Kidd J. F., Fogarty K. E., Tuft R. A., Thorn P. The role of Ca2+ feedback in shaping InsP3-evoked Ca2+ signals in mouse pancreatic acinar cells. J Physiol. 1999 Oct 1;520(Pt 1):187–201. doi: 10.1111/j.1469-7793.1999.00187.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Lee M. G., Xu X., Zeng W., Diaz J., Wojcikiewicz R. J., Kuo T. H., Wuytack F., Racymaekers L., Muallem S. Polarized expression of Ca2+ channels in pancreatic and salivary gland cells. Correlation with initiation and propagation of [Ca2+]i waves. J Biol Chem. 1997 Jun 20;272(25):15765–15770. doi: 10.1074/jbc.272.25.15765. [DOI] [PubMed] [Google Scholar]
  16. Mak D. O., Foskett J. K. Single-channel kinetics, inactivation, and spatial distribution of inositol trisphosphate (IP3) receptors in Xenopus oocyte nucleus. J Gen Physiol. 1997 May;109(5):571–587. doi: 10.1085/jgp.109.5.571. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Missiaen L., Parys J. B., Sienaert I., Maes K., Kunzelmann K., Takahashi M., Tanzawa K., De Smedt H. Functional properties of the type-3 InsP3 receptor in 16HBE14o- bronchial mucosal cells. J Biol Chem. 1998 Apr 10;273(15):8983–8986. doi: 10.1074/jbc.273.15.8983. [DOI] [PubMed] [Google Scholar]
  18. Miyakawa T., Maeda A., Yamazawa T., Hirose K., Kurosaki T., Iino M. Encoding of Ca2+ signals by differential expression of IP3 receptor subtypes. EMBO J. 1999 Mar 1;18(5):1303–1308. doi: 10.1093/emboj/18.5.1303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Nelson M. T., Cheng H., Rubart M., Santana L. F., Bonev A. D., Knot H. J., Lederer W. J. Relaxation of arterial smooth muscle by calcium sparks. Science. 1995 Oct 27;270(5236):633–637. doi: 10.1126/science.270.5236.633. [DOI] [PubMed] [Google Scholar]
  20. Newton C. L., Mignery G. A., Südhof T. C. Co-expression in vertebrate tissues and cell lines of multiple inositol 1,4,5-trisphosphate (InsP3) receptors with distinct affinities for InsP3. J Biol Chem. 1994 Nov 18;269(46):28613–28619. [PubMed] [Google Scholar]
  21. Parys J. B., de Smedt H., Missiaen L., Bootman M. D., Sienaert I., Casteels R. Rat basophilic leukemia cells as model system for inositol 1,4,5-trisphosphate receptor IV, a receptor of the type II family: functional comparison and immunological detection. Cell Calcium. 1995 Apr;17(4):239–249. doi: 10.1016/0143-4160(95)90070-5. [DOI] [PubMed] [Google Scholar]
  22. Petersen O. H. Stimulus-secretion coupling: cytoplasmic calcium signals and the control of ion channels in exocrine acinar cells. J Physiol. 1992 Mar;448:1–51. doi: 10.1113/jphysiol.1992.sp019028. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ramos-Franco J., Fill M., Mignery G. A. Isoform-specific function of single inositol 1,4,5-trisphosphate receptor channels. Biophys J. 1998 Aug;75(2):834–839. doi: 10.1016/S0006-3495(98)77572-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Rizzuto R., Pinton P., Carrington W., Fay F. S., Fogarty K. E., Lifshitz L. M., Tuft R. A., Pozzan T. Close contacts with the endoplasmic reticulum as determinants of mitochondrial Ca2+ responses. Science. 1998 Jun 12;280(5370):1763–1766. doi: 10.1126/science.280.5370.1763. [DOI] [PubMed] [Google Scholar]
  25. Sun X. P., Callamaras N., Marchant J. S., Parker I. A continuum of InsP3-mediated elementary Ca2+ signalling events in Xenopus oocytes. J Physiol. 1998 May 15;509(Pt 1):67–80. doi: 10.1111/j.1469-7793.1998.067bo.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Taylor C. W. Inositol trisphosphate receptors: Ca2+-modulated intracellular Ca2+ channels. Biochim Biophys Acta. 1998 Dec 8;1436(1-2):19–33. doi: 10.1016/s0005-2760(98)00122-2. [DOI] [PubMed] [Google Scholar]
  27. Thomas D., Lipp P., Berridge M. J., Bootman M. D. Hormone-evoked elementary Ca2+ signals are not stereotypic, but reflect activation of different size channel clusters and variable recruitment of channels within a cluster. J Biol Chem. 1998 Oct 16;273(42):27130–27136. doi: 10.1074/jbc.273.42.27130. [DOI] [PubMed] [Google Scholar]
  28. Thorn P., Gerasimenko O., Petersen O. H. Cyclic ADP-ribose regulation of ryanodine receptors involved in agonist evoked cytosolic Ca2+ oscillations in pancreatic acinar cells. EMBO J. 1994 May 1;13(9):2038–2043. doi: 10.1002/j.1460-2075.1994.tb06478.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Thorn P., Lawrie A. M., Smith P. M., Gallacher D. V., Petersen O. H. Local and global cytosolic Ca2+ oscillations in exocrine cells evoked by agonists and inositol trisphosphate. Cell. 1993 Aug 27;74(4):661–668. doi: 10.1016/0092-8674(93)90513-p. [DOI] [PubMed] [Google Scholar]
  30. Thorn P., Moreton R., Berridge M. Multiple, coordinated Ca2+ -release events underlie the inositol trisphosphate-induced local Ca2+ spikes in mouse pancreatic acinar cells. EMBO J. 1996 Mar 1;15(5):999–1003. [PMC free article] [PubMed] [Google Scholar]
  31. Thorn P., Petersen O. H. Activation of nonselective cation channels by physiological cholecystokinin concentrations in mouse pancreatic acinar cells. J Gen Physiol. 1992 Jul;100(1):11–25. doi: 10.1085/jgp.100.1.11. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wakui M., Petersen O. H. Cytoplasmic Ca2+ oscillations evoked by acetylcholine or intracellular infusion of inositol trisphosphate or Ca2+ can be inhibited by internal Ca2+. FEBS Lett. 1990 Apr 24;263(2):206–208. doi: 10.1016/0014-5793(90)81374-w. [DOI] [PubMed] [Google Scholar]
  33. Wojcikiewicz R. J. Type I, II, and III inositol 1,4,5-trisphosphate receptors are unequally susceptible to down-regulation and are expressed in markedly different proportions in different cell types. J Biol Chem. 1995 May 12;270(19):11678–11683. doi: 10.1074/jbc.270.19.11678. [DOI] [PubMed] [Google Scholar]
  34. Yao Y., Choi J., Parker I. Quantal puffs of intracellular Ca2+ evoked by inositol trisphosphate in Xenopus oocytes. J Physiol. 1995 Feb 1;482(Pt 3):533–553. doi: 10.1113/jphysiol.1995.sp020538. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Yule D. I., Ernst S. A., Ohnishi H., Wojcikiewicz R. J. Evidence that zymogen granules are not a physiologically relevant calcium pool. Defining the distribution of inositol 1,4,5-trisphosphate receptors in pancreatic acinar cells. J Biol Chem. 1997 Apr 4;272(14):9093–9098. doi: 10.1074/jbc.272.14.9093. [DOI] [PubMed] [Google Scholar]
  36. Zou H., Lifshitz L. M., Tuft R. A., Fogarty K. E., Singer J. J. Imaging Ca(2+) entering the cytoplasm through a single opening of a plasma membrane cation channel. J Gen Physiol. 1999 Oct;114(4):575–588. doi: 10.1085/jgp.114.4.575. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Biophysical Journal are provided here courtesy of The Biophysical Society

RESOURCES