Skip to main content
NCBI home page
The EMBO Journal logoLink to The EMBO Journal
. 1999 Jun 15;18(12):3222–3231. doi: 10.1093/emboj/18.12.3222

The mechanism mediating regenerative intercellular Ca2+ waves in the blowfly salivary gland.

B Zimmermann 1, B Walz 1
PMCID: PMC1171403  PMID: 10369663

Abstract

Intercellular Ca2+ signaling in intact salivary glands of the blowfly Calliphora erythrocephala was studied by fluorimetric digital imaging combined with microinjection of putative messenger molecules. Iontophoretic injection of D-myo-inositol 1,4, 5-trisphosphate (InsP3) into salivary gland cells evoked regenerative intercellular Ca2+ waves that spread through the impaled cell and several rows of surrounding cells. Ca2+ increases induced by microinjection of Ca2+ ions were confined to the injected cells and their nearest neighbors. Depletion of intracellular Ca2+ stores by thapsigargin pre-treatment did not alter the time course of the Ca2+ increase caused by Ca2+ injection. However, activation of Ca2+ release became clearly evident when Ca2+ was injected in the presence of serotonin (5-HT). Under these conditions, injection of Ca2+ triggered intercellular Ca2+ waves that consecutively passed through >10 cells. The phospholipase C inhibitor U73122 blocked 5-HT-induced Ca2+ increases but did not affect InsP3-dependent Ca2+ spiking and intercellular Ca2+ wave propagation. The results demonstrate that propagation of agonist-evoked Ca2+ waves in the blowfly salivary gland requires supra-basal [InsP3] but does not depend on feedback activation of phospholipase C. We conclude that the intra- and intercellular transmission of these Ca2+ waves is mediated by diffusion of Ca2+ and Ca2+-induced Ca2+ release via the InsP3 receptor channel.

Full Text

The Full Text of this article is available as a PDF (618.0 KB).

Selected References

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

  1. Allbritton N. L., Meyer T., Stryer L. Range of messenger action of calcium ion and inositol 1,4,5-trisphosphate. Science. 1992 Dec 11;258(5089):1812–1815. doi: 10.1126/science.1465619. [DOI] [PubMed] [Google Scholar]
  2. Atri A., Amundson J., Clapham D., Sneyd J. A single-pool model for intracellular calcium oscillations and waves in the Xenopus laevis oocyte. Biophys J. 1993 Oct;65(4):1727–1739. doi: 10.1016/S0006-3495(93)81191-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berridge M. J., Dawson R. M., Downes C. P., Heslop J. P., Irvine R. F. Changes in the levels of inositol phosphates after agonist-dependent hydrolysis of membrane phosphoinositides. Biochem J. 1983 May 15;212(2):473–482. doi: 10.1042/bj2120473. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berridge M. J. Inositol trisphosphate and calcium signalling. Nature. 1993 Jan 28;361(6410):315–325. doi: 10.1038/361315a0. [DOI] [PubMed] [Google Scholar]
  5. Berridge M. J. Rapid accumulation of inositol trisphosphate reveals that agonists hydrolyse polyphosphoinositides instead of phosphatidylinositol. Biochem J. 1983 Jun 15;212(3):849–858. doi: 10.1042/bj2120849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bezprozvanny I., Watras J., Ehrlich B. E. Bell-shaped calcium-response curves of Ins(1,4,5)P3- and calcium-gated channels from endoplasmic reticulum of cerebellum. Nature. 1991 Jun 27;351(6329):751–754. doi: 10.1038/351751a0. [DOI] [PubMed] [Google Scholar]
  7. Bird G. S., Obie J. F., Putney J. W., Jr Effect of cytoplasmic Ca2+ on (1,4,5)IP3 formation in vasopressin-activated hepatocytes. Cell Calcium. 1997 Mar;21(3):253–256. doi: 10.1016/s0143-4160(97)90049-x. [DOI] [PubMed] [Google Scholar]
  8. Bleasdale J. E., Thakur N. R., Gremban R. S., Bundy G. L., Fitzpatrick F. A., Smith R. J., Bunting S. Selective inhibition of receptor-coupled phospholipase C-dependent processes in human platelets and polymorphonuclear neutrophils. J Pharmacol Exp Ther. 1990 Nov;255(2):756–768. [PubMed] [Google Scholar]
  9. Boitano S., Dirksen E. R., Sanderson M. J. Intercellular propagation of calcium waves mediated by inositol trisphosphate. Science. 1992 Oct 9;258(5080):292–295. doi: 10.1126/science.1411526. [DOI] [PubMed] [Google Scholar]
  10. Charles A. C., Merrill J. E., Dirksen E. R., Sanderson M. J. Intercellular signaling in glial cells: calcium waves and oscillations in response to mechanical stimulation and glutamate. Neuron. 1991 Jun;6(6):983–992. doi: 10.1016/0896-6273(91)90238-u. [DOI] [PubMed] [Google Scholar]
  11. Churchill G. C., Atkinson M. M., Louis C. F. Mechanical stimulation initiates cell-to-cell calcium signaling in ovine lens epithelial cells. J Cell Sci. 1996 Feb;109(Pt 2):355–365. doi: 10.1242/jcs.109.2.355. [DOI] [PubMed] [Google Scholar]
  12. Churchill G. C., Louis C. F. Roles of Ca2+, inositol trisphosphate and cyclic ADP-ribose in mediating intercellular Ca2+ signaling in sheep lens cells. J Cell Sci. 1998 May;111(Pt 9):1217–1225. doi: 10.1242/jcs.111.9.1217. [DOI] [PubMed] [Google Scholar]
  13. Cornell-Bell A. H., Finkbeiner S. M., Cooper M. S., Smith S. J. Glutamate induces calcium waves in cultured astrocytes: long-range glial signaling. Science. 1990 Jan 26;247(4941):470–473. doi: 10.1126/science.1967852. [DOI] [PubMed] [Google Scholar]
  14. Cuthbertson K. S., Chay T. R. Modelling receptor-controlled intracellular calcium oscillators. Cell Calcium. 1991 Feb-Mar;12(2-3):97–109. doi: 10.1016/0143-4160(91)90012-4. [DOI] [PubMed] [Google Scholar]
  15. De Young G. W., Keizer J. A single-pool inositol 1,4,5-trisphosphate-receptor-based model for agonist-stimulated oscillations in Ca2+ concentration. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9895–9899. doi: 10.1073/pnas.89.20.9895. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. DeLisle S., Welsh M. J. Inositol trisphosphate is required for the propagation of calcium waves in Xenopus oocytes. J Biol Chem. 1992 Apr 25;267(12):7963–7966. [PubMed] [Google Scholar]
  17. Demer L. L., Wortham C. M., Dirksen E. R., Sanderson M. J. Mechanical stimulation induces intercellular calcium signaling in bovine aortic endothelial cells. Am J Physiol. 1993 Jun;264(6 Pt 2):H2094–H2102. doi: 10.1152/ajpheart.1993.264.6.H2094. [DOI] [PubMed] [Google Scholar]
  18. Domenighetti A. A., Bény J. L., Chabaud F., Frieden M. An intercellular regenerative calcium wave in porcine coronary artery endothelial cells in primary culture. J Physiol. 1998 Nov 15;513(Pt 1):103–116. doi: 10.1111/j.1469-7793.1998.103by.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Fain J. N., Berridge M. J. Relationship between hormonal activation of phosphatidylinositol hydrolysis, fluid secretion and calcium flux in the blowfly salivary gland. Biochem J. 1979 Jan 15;178(1):45–58. doi: 10.1042/bj1780045. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Finch E. A., Turner T. J., Goldin S. M. Calcium as a coagonist of inositol 1,4,5-trisphosphate-induced calcium release. Science. 1991 Apr 19;252(5004):443–446. doi: 10.1126/science.2017683. [DOI] [PubMed] [Google Scholar]
  21. Finkbeiner S. Calcium waves in astrocytes-filling in the gaps. Neuron. 1992 Jun;8(6):1101–1108. doi: 10.1016/0896-6273(92)90131-v. [DOI] [PubMed] [Google Scholar]
  22. Goldbeter A., Dupont G., Berridge M. J. Minimal model for signal-induced Ca2+ oscillations and for their frequency encoding through protein phosphorylation. Proc Natl Acad Sci U S A. 1990 Feb;87(4):1461–1465. doi: 10.1073/pnas.87.4.1461. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  24. Hajnóczky G., Thomas A. P. Minimal requirements for calcium oscillations driven by the IP3 receptor. EMBO J. 1997 Jun 16;16(12):3533–3543. doi: 10.1093/emboj/16.12.3533. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Harootunian A. T., Kao J. P., Paranjape S., Tsien R. Y. Generation of calcium oscillations in fibroblasts by positive feedback between calcium and IP3. Science. 1991 Jan 4;251(4989):75–78. doi: 10.1126/science.1986413. [DOI] [PubMed] [Google Scholar]
  26. Iino M. Biphasic Ca2+ dependence of inositol 1,4,5-trisphosphate-induced Ca release in smooth muscle cells of the guinea pig taenia caeci. J Gen Physiol. 1990 Jun;95(6):1103–1122. doi: 10.1085/jgp.95.6.1103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Jaffe L. F. Classes and mechanisms of calcium waves. Cell Calcium. 1993 Nov;14(10):736–745. doi: 10.1016/0143-4160(93)90099-r. [DOI] [PubMed] [Google Scholar]
  28. Jaffe L. F. The path of calcium in cytosolic calcium oscillations: a unifying hypothesis. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9883–9887. doi: 10.1073/pnas.88.21.9883. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Lechleiter J. D., Clapham D. E. Molecular mechanisms of intracellular calcium excitability in X. laevis oocytes. Cell. 1992 Apr 17;69(2):283–294. doi: 10.1016/0092-8674(92)90409-6. [DOI] [PubMed] [Google Scholar]
  30. Lechleiter J., Girard S., Peralta E., Clapham D. Spiral calcium wave propagation and annihilation in Xenopus laevis oocytes. Science. 1991 Apr 5;252(5002):123–126. doi: 10.1126/science.2011747. [DOI] [PubMed] [Google Scholar]
  31. Meyer T., Stryer L. Calcium spiking. Annu Rev Biophys Biophys Chem. 1991;20:153–174. doi: 10.1146/annurev.bb.20.060191.001101. [DOI] [PubMed] [Google Scholar]
  32. Nathanson M. H., Burgstahler A. D., Mennone A., Fallon M. B., Gonzalez C. B., Saez J. C. Ca2+ waves are organized among hepatocytes in the intact organ. Am J Physiol. 1995 Jul;269(1 Pt 1):G167–G171. doi: 10.1152/ajpgi.1995.269.1.G167. [DOI] [PubMed] [Google Scholar]
  33. Newman E. A., Zahs K. R. Calcium waves in retinal glial cells. Science. 1997 Feb 7;275(5301):844–847. doi: 10.1126/science.275.5301.844. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Parker I., Ivorra I. Inhibition by Ca2+ of inositol trisphosphate-mediated Ca2+ liberation: a possible mechanism for oscillatory release of Ca2+. Proc Natl Acad Sci U S A. 1990 Jan;87(1):260–264. doi: 10.1073/pnas.87.1.260. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Rhee S. G., Suh P. G., Ryu S. H., Lee S. Y. Studies of inositol phospholipid-specific phospholipase C. Science. 1989 May 5;244(4904):546–550. doi: 10.1126/science.2541501. [DOI] [PubMed] [Google Scholar]
  36. Robb-Gaspers L. D., Thomas A. P. Coordination of Ca2+ signaling by intercellular propagation of Ca2+ waves in the intact liver. J Biol Chem. 1995 Apr 7;270(14):8102–8107. doi: 10.1074/jbc.270.14.8102. [DOI] [PubMed] [Google Scholar]
  37. Sanderson M. J., Charles A. C., Boitano S., Dirksen E. R. Mechanisms and function of intercellular calcium signaling. Mol Cell Endocrinol. 1994 Jan;98(2):173–187. doi: 10.1016/0303-7207(94)90136-8. [DOI] [PubMed] [Google Scholar]
  38. Sanderson M. J., Charles A. C., Dirksen E. R. Mechanical stimulation and intercellular communication increases intracellular Ca2+ in epithelial cells. Cell Regul. 1990 Jul;1(8):585–596. doi: 10.1091/mbc.1.8.585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Sneyd J., Charles A. C., Sanderson M. J. A model for the propagation of intercellular calcium waves. Am J Physiol. 1994 Jan;266(1 Pt 1):C293–C302. doi: 10.1152/ajpcell.1994.266.1.C293. [DOI] [PubMed] [Google Scholar]
  40. Sáez J. C., Connor J. A., Spray D. C., Bennett M. V. Hepatocyte gap junctions are permeable to the second messenger, inositol 1,4,5-trisphosphate, and to calcium ions. Proc Natl Acad Sci U S A. 1989 Apr;86(8):2708–2712. doi: 10.1073/pnas.86.8.2708. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Tordjmann T., Berthon B., Claret M., Combettes L. Coordinated intercellular calcium waves induced by noradrenaline in rat hepatocytes: dual control by gap junction permeability and agonist. EMBO J. 1997 Sep 1;16(17):5398–5407. doi: 10.1093/emboj/16.17.5398. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. 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]
  43. Wang S. S., Thompson S. H. Local positive feedback by calcium in the propagation of intracellular calcium waves. Biophys J. 1995 Nov;69(5):1683–1697. doi: 10.1016/S0006-3495(95)80086-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Xia S. L., Ferrier J. Propagation of a calcium pulse between osteoblastic cells. Biochem Biophys Res Commun. 1992 Aug 14;186(3):1212–1219. doi: 10.1016/s0006-291x(05)81535-9. [DOI] [PubMed] [Google Scholar]
  45. Yule D. I., Stuenkel E., Williams J. A. Intercellular calcium waves in rat pancreatic acini: mechanism of transmission. Am J Physiol. 1996 Oct;271(4 Pt 1):C1285–C1294. doi: 10.1152/ajpcell.1996.271.4.C1285. [DOI] [PubMed] [Google Scholar]
  46. Zimmermann B. Calcium store depletion activates two distinct calcium entry pathways in secretory cells of the blowfly salivary gland. Cell Calcium. 1998 Jan;23(1):53–63. doi: 10.1016/s0143-4160(98)90074-4. [DOI] [PubMed] [Google Scholar]
  47. Zimmermann B., Walz B. Serotonin-induced intercellular calcium waves in salivary glands of the blowfly Calliphora erythrocephala. J Physiol. 1997 Apr 1;500(Pt 1):17–28. doi: 10.1113/jphysiol.1997.sp021995. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES