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. 2001 Jul;81(1):57–65. doi: 10.1016/S0006-3495(01)75679-2

Membrane-initiated Ca(2+) signals are reshaped during propagation to subcellular regions.

W J Koopman 1, W J Scheenen 1, R J Errington 1, P H Willems 1, R J Bindels 1, E W Roubos 1, B G Jenks 1
PMCID: PMC1301491  PMID: 11423394

Abstract

An important aspect of Ca(2+) signaling is the ability of cells to generate intracellular Ca(2+) waves. In this study we have analyzed the cellular and subcellular kinetics of Ca(2+) waves in a neuroendocrine transducer cell, the melanotrope of Xenopus laevis, using the ratiometric Ca(2+) probe indo-1 and video-rate UV confocal laser-scanning microscopy. The purpose of the present study was to investigate how local Ca(2+) changes contribute to a global Ca(2+) signal; subsequently we quantified how a Ca(2+) wave is kinetically reshaped as it is propagated through the cell. The combined kinetics of all subcellular Ca(2+) signals determined the shape of the total cellular Ca(2+) signal, but each subcellular contribution to the cellular signal was not constant in time. Near the plasma membrane, [Ca(2+)](i) increased and decreased rapidly, processes that can be described by a linear and exponential function, respectively. In more central parts of the cell slower kinetics were observed that were best described by a Hill equation. This reshaping of the Ca(2+) wave was modeled with an equation derived from a low-pass RC filter. We propose that the differences in spatial kinetics of the Ca(2+) signal serves as a mechanism by which the same cellular Ca(2+) signal carries different regulatory information to different subcellular regions of the cell, thus evoking differential cellular responses.

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Selected References

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  1. Berridge M. J. The AM and FM of calcium signalling. Nature. 1997 Apr 24;386(6627):759–760. doi: 10.1038/386759a0. [DOI] [PubMed] [Google Scholar]
  2. Bito H., Deisseroth K., Tsien R. W. CREB phosphorylation and dephosphorylation: a Ca(2+)- and stimulus duration-dependent switch for hippocampal gene expression. Cell. 1996 Dec 27;87(7):1203–1214. doi: 10.1016/s0092-8674(00)81816-4. [DOI] [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. D., Berridge M. J. The elemental principles of calcium signaling. Cell. 1995 Dec 1;83(5):675–678. doi: 10.1016/0092-8674(95)90179-5. [DOI] [PubMed] [Google Scholar]
  5. Burgoyne R. D., Morgan A. Calcium sensors in regulated exocytosis. Cell Calcium. 1998 Nov-Dec;24(5-6):367–376. doi: 10.1016/s0143-4160(98)90060-4. [DOI] [PubMed] [Google Scholar]
  6. Chin D., Means A. R. Calmodulin: a prototypical calcium sensor. Trends Cell Biol. 2000 Aug;10(8):322–328. doi: 10.1016/s0962-8924(00)01800-6. [DOI] [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. Dotman C. H., Maia A., Jenks B. G., Roubos E. W. Sauvagine and TRH differentially stimulate proopiomelanocortin biosynthesis in the Xenopus laevis intermediate pituitary. Neuroendocrinology. 1997 Aug;66(2):106–113. doi: 10.1159/000127226. [DOI] [PubMed] [Google Scholar]
  10. Douglas W. W., Shibuya I. Calcium signals in melanotrophs and their relation to autonomous secretion and its modification by inhibitory and stimulatory ligands. Ann N Y Acad Sci. 1993 May 31;680:229–245. doi: 10.1111/j.1749-6632.1993.tb19687.x. [DOI] [PubMed] [Google Scholar]
  11. Finch E. A., Augustine G. J. Local calcium signalling by inositol-1,4,5-trisphosphate in Purkinje cell dendrites. Nature. 1998 Dec 24;396(6713):753–756. doi: 10.1038/25541. [DOI] [PubMed] [Google Scholar]
  12. Ince C., van Dissel J. T., Diesselhoff M. M. A teflon culture dish for high-magnification microscopy and measurements in single cells. Pflugers Arch. 1985 Mar;403(3):240–244. doi: 10.1007/BF00583594. [DOI] [PubMed] [Google Scholar]
  13. Kasai H. Comparative biology of Ca2+-dependent exocytosis: implications of kinetic diversity for secretory function. Trends Neurosci. 1999 Feb;22(2):88–93. doi: 10.1016/s0166-2236(98)01293-4. [DOI] [PubMed] [Google Scholar]
  14. Koopman W. J., Hink M. A., Visser A. J., Roubos E. W., Jenks B. G. Evidence that Ca2+-waves in Xenopus melanotropes depend on calcium-induced calcium release: a fluorescence correlation microscopy and linescanning study. Cell Calcium. 1999 Jul-Aug;26(1-2):59–67. doi: 10.1054/ceca.1999.0051. [DOI] [PubMed] [Google Scholar]
  15. Koopman W. J., Scheenen W. J., Roubos E. W., Jenks B. G. Kinetics of calcium steps underlying calcium oscillations in melanotrope cells of Xenopus laevis. Cell Calcium. 1997 Sep;22(3):167–178. doi: 10.1016/s0143-4160(97)90010-5. [DOI] [PubMed] [Google Scholar]
  16. Li W., Llopis J., Whitney M., Zlokarnik G., Tsien R. Y. Cell-permeant caged InsP3 ester shows that Ca2+ spike frequency can optimize gene expression. Nature. 1998 Apr 30;392(6679):936–941. doi: 10.1038/31965. [DOI] [PubMed] [Google Scholar]
  17. Lieste J. R., Koopman W. J., Reynen V. C., Scheenen W. J., Jenks B. G., Roubos E. W. Action currents generate stepwise intracellular Ca2+ patterns in a neuroendocrine cell. J Biol Chem. 1998 Oct 2;273(40):25686–25694. doi: 10.1074/jbc.273.40.25686. [DOI] [PubMed] [Google Scholar]
  18. López-López J. R., Shacklock P. S., Balke C. W., Wier W. G. Local calcium transients triggered by single L-type calcium channel currents in cardiac cells. Science. 1995 May 19;268(5213):1042–1045. doi: 10.1126/science.7754383. [DOI] [PubMed] [Google Scholar]
  19. Naraghi M., Müller T. H., Neher E. Two-dimensional determination of the cellular Ca2+ binding in bovine chromaffin cells. Biophys J. 1998 Oct;75(4):1635–1647. doi: 10.1016/S0006-3495(98)77606-4. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Petersen O. H., Burdakov D., Tepikin A. V. Polarity in intracellular calcium signaling. Bioessays. 1999 Oct;21(10):851–860. doi: 10.1002/(SICI)1521-1878(199910)21:10<851::AID-BIES7>3.0.CO;2-F. [DOI] [PubMed] [Google Scholar]
  21. Scheenen W. J., Jenks B. G., Roubos E. W., Willems P. H. Spontaneous calcium oscillations in Xenopus laevis melanotrope cells are mediated by omega-conotoxin sensitive calcium channels. Cell Calcium. 1994 Jan;15(1):36–44. doi: 10.1016/0143-4160(94)90102-3. [DOI] [PubMed] [Google Scholar]
  22. Scheenen W. J., Jenks B. G., Willems P. H., Roubos E. W. Action of stimulatory and inhibitory alpha-MSH secretagogues on spontaneous calcium oscillations in melanotrope cells of Xenopus laevis. Pflugers Arch. 1994 Jun;427(3-4):244–251. doi: 10.1007/BF00374530. [DOI] [PubMed] [Google Scholar]
  23. Scheenen W. J., Jenks B. G., van Dinter R. J., Roubos E. W. Spatial and temporal aspects of Ca2+ oscillations in Xenopus laevis melanotrope cells. Cell Calcium. 1996 Mar;19(3):219–227. doi: 10.1016/s0143-4160(96)90023-8. [DOI] [PubMed] [Google Scholar]
  24. Scheenen W. J., de Koning H. P., Jenks B. G., Vaudry H., Roubos E. W. The secretion of alpha-MSH from xenopus melanotropes involves calcium influx through omega-conotoxin-sensitive voltage-operated calcium channels. J Neuroendocrinol. 1994 Aug;6(4):457–464. doi: 10.1111/j.1365-2826.1994.tb00607.x. [DOI] [PubMed] [Google Scholar]
  25. Sham J. S. Ca2+ release-induced inactivation of Ca2+ current in rat ventricular myocytes: evidence for local Ca2+ signalling. J Physiol. 1997 Apr 15;500(Pt 2):285–295. doi: 10.1113/jphysiol.1997.sp022020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Shibuya I., Douglas W. W. Spontaneous cytosolic calcium pulsing detected in Xenopus melanotrophs: modulation by secreto-inhibitory and stimulant ligands. Endocrinology. 1993 May;132(5):2166–2175. doi: 10.1210/endo.132.5.8386613. [DOI] [PubMed] [Google Scholar]
  27. Thomas P., Wong J. G., Almers W. Millisecond studies of secretion in single rat pituitary cells stimulated by flash photolysis of caged Ca2+. EMBO J. 1993 Jan;12(1):303–306. doi: 10.1002/j.1460-2075.1993.tb05657.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. 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]
  30. Tse F. W., Tse A., Hille B., Horstmann H., Almers W. Local Ca2+ release from internal stores controls exocytosis in pituitary gonadotrophs. Neuron. 1997 Jan;18(1):121–132. doi: 10.1016/s0896-6273(01)80051-9. [DOI] [PubMed] [Google Scholar]

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