Skip to main content
NCBI home page
Biophysical Journal logoLink to Biophysical Journal
. 1995 May;68(5):1752–1766. doi: 10.1016/S0006-3495(95)80352-8

[Ca2+]i oscillations in sympathetic neurons: an experimental test of a theoretical model.

D D Friel 1
PMCID: PMC1282078  PMID: 7612818

Abstract

[Ca2+]i oscillations have been described in a variety of cells. This study focuses on caffeine-induced [Ca2+]i oscillations in sympathetic neurons. Previous work has shown that these oscillations require Ca2+ entry from the extracellular medium and Ca(2+)-induced Ca2+ release from a caffeine- and ryanodine-sensitive store. The aim of the study was to understand the mechanism responsible for the oscillations. As a starting point, [Ca2+]i relaxations were examined after membrane depolarization and exposure to caffeine. For both stimuli, post-stimulus relaxations could be described by the sum of two decaying exponential functions, consistent with a one-pool system in which Ca2+ transport between compartments is regulated by linear Ca2+ pumps and leaks. After modifying the store to include a [Ca2+]i-sensitive leak, the model also exhibits oscillations such as those observed experimentally. The model was tested by comparing measured and predicted net Ca2+ fluxes during the oscillatory cycle. Three independent fluxes were measured, describing the rates of 1) Ca2+ entry across the plasma membrane, 2) Ca2+ release by the internal store, and 3) Ca2+ extrusion across the plasma membrane and uptake by the internal store. Starting with estimates of the model parameters deduced from post-stimulus relaxations and the rapid upstroke, a set of parameter values was found that provides a good description of [Ca2+]i throughout the oscillatory cycle. With the same parameter values, there was also good agreement between the measured and simulated net fluxes. Thus, a one-pool model with a single [Ca2+]i-sensitive Ca2+ permeability is adequate to account for many of the quantitative properties of steady-state [Ca2+]i oscillations in sympathetic neurons. Inactivation of the intracellular Ca2+ permeability, cooperative nonlinear Ca2+ uptake and extrusion mechanisms, and functional links between plasma membrane Ca2+ transport and the internal store are not required.

Full text

PDF
1753

Images in this article

1762FIGURE 12
on p.1762

Selected References

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

  1. 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]
  2. Balke C. W., Egan T. M., Wier W. G. Processes that remove calcium from the cytoplasm during excitation-contraction coupling in intact rat heart cells. J Physiol. 1994 Feb 1;474(3):447–462. doi: 10.1113/jphysiol.1994.sp020036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baró I., O'Neill S. C., Eisner D. A. Changes of intracellular [Ca2+] during refilling of sarcoplasmic reticulum in rat ventricular and vascular smooth muscle. J Physiol. 1993 Jun;465:21–41. doi: 10.1113/jphysiol.1993.sp019664. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berridge M. J. Cytoplasmic calcium oscillations: a two pool model. Cell Calcium. 1991 Feb-Mar;12(2-3):63–72. doi: 10.1016/0143-4160(91)90009-4. [DOI] [PubMed] [Google Scholar]
  5. Berridge M. J. Inositol trisphosphate and calcium signalling. Nature. 1993 Jan 28;361(6410):315–325. doi: 10.1038/361315a0. [DOI] [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. 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]
  8. 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]
  9. Dupont G., Berridge M. J., Goldbeter A. Signal-induced Ca2+ oscillations: properties of a model based on Ca(2+)-induced Ca2+ release. Cell Calcium. 1991 Feb-Mar;12(2-3):73–85. doi: 10.1016/0143-4160(91)90010-c. [DOI] [PubMed] [Google Scholar]
  10. Dupont G., Goldbeter A. One-pool model for Ca2+ oscillations involving Ca2+ and inositol 1,4,5-trisphosphate as co-agonists for Ca2+ release. Cell Calcium. 1993 Apr;14(4):311–322. doi: 10.1016/0143-4160(93)90052-8. [DOI] [PubMed] [Google Scholar]
  11. Fewtrell C. Ca2+ oscillations in non-excitable cells. Annu Rev Physiol. 1993;55:427–454. doi: 10.1146/annurev.ph.55.030193.002235. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Friel D. D., Tsien R. W. A caffeine- and ryanodine-sensitive Ca2+ store in bullfrog sympathetic neurones modulates effects of Ca2+ entry on [Ca2+]i. J Physiol. 1992 May;450:217–246. doi: 10.1113/jphysiol.1992.sp019125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Friel D. D., Tsien R. W. An FCCP-sensitive Ca2+ store in bullfrog sympathetic neurons and its participation in stimulus-evoked changes in [Ca2+]i. J Neurosci. 1994 Jul;14(7):4007–4024. doi: 10.1523/JNEUROSCI.14-07-04007.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Friel D. D., Tsien R. W. Phase-dependent contributions from Ca2+ entry and Ca2+ release to caffeine-induced [Ca2+]i oscillations in bullfrog sympathetic neurons. Neuron. 1992 Jun;8(6):1109–1125. doi: 10.1016/0896-6273(92)90132-w. [DOI] [PubMed] [Google Scholar]
  16. Galione A. Cyclic ADP-ribose: a new way to control calcium. Science. 1993 Jan 15;259(5093):325–326. doi: 10.1126/science.8380506. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. Gurney A. M., Charnet P., Pye J. M., Nargeot J. Augmentation of cardiac calcium current by flash photolysis of intracellular caged-Ca2+ molecules. Nature. 1989 Sep 7;341(6237):65–68. doi: 10.1038/341065a0. [DOI] [PubMed] [Google Scholar]
  19. Györke S., Fill M. Ryanodine receptor adaptation: control mechanism of Ca(2+)-induced Ca2+ release in heart. Science. 1993 May 7;260(5109):807–809. doi: 10.1126/science.8387229. [DOI] [PubMed] [Google Scholar]
  20. Hernández-Cruz A., Sala F., Adams P. R. Subcellular calcium transients visualized by confocal microscopy in a voltage-clamped vertebrate neuron. Science. 1990 Feb 16;247(4944):858–862. doi: 10.1126/science.2154851. [DOI] [PubMed] [Google Scholar]
  21. Hille B., Tse A., Tse F. W., Almers W. Calcium oscillations and exocytosis in pituitary gonadotropes. Ann N Y Acad Sci. 1994 Mar 9;710:261–270. doi: 10.1111/j.1749-6632.1994.tb26634.x. [DOI] [PubMed] [Google Scholar]
  22. Hoth M., Penner R. Depletion of intracellular calcium stores activates a calcium current in mast cells. Nature. 1992 Jan 23;355(6358):353–356. doi: 10.1038/355353a0. [DOI] [PubMed] [Google Scholar]
  23. Hove-Madsen L., Bers D. M. Passive Ca buffering and SR Ca uptake in permeabilized rabbit ventricular myocytes. Am J Physiol. 1993 Mar;264(3 Pt 1):C677–C686. doi: 10.1152/ajpcell.1993.264.3.C677. [DOI] [PubMed] [Google Scholar]
  24. Hua S. Y., Nohmi M., Kuba K. Characteristics of Ca2+ release induced by Ca2+ influx in cultured bullfrog sympathetic neurones. J Physiol. 1993 May;464:245–272. doi: 10.1113/jphysiol.1993.sp019633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Jacob R. Agonist-stimulated divalent cation entry into single cultured human umbilical vein endothelial cells. J Physiol. 1990 Feb;421:55–77. doi: 10.1113/jphysiol.1990.sp017933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Jacob R. Calcium oscillations in electrically non-excitable cells. Biochim Biophys Acta. 1990 May 22;1052(3):427–438. doi: 10.1016/0167-4889(90)90152-4. [DOI] [PubMed] [Google Scholar]
  27. Jacob R., Merritt J. E., Hallam T. J., Rink T. J. Repetitive spikes in cytoplasmic calcium evoked by histamine in human endothelial cells. Nature. 1988 Sep 1;335(6185):40–45. doi: 10.1038/335040a0. [DOI] [PubMed] [Google Scholar]
  28. Jones S. W., Marks T. N. Calcium currents in bullfrog sympathetic neurons. I. Activation kinetics and pharmacology. J Gen Physiol. 1989 Jul;94(1):151–167. doi: 10.1085/jgp.94.1.151. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Kovacs L., Rios E., Schneider M. F. Measurement and modification of free calcium transients in frog skeletal muscle fibres by a metallochromic indicator dye. J Physiol. 1983 Oct;343:161–196. doi: 10.1113/jphysiol.1983.sp014887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Kuba K., Nishi S. Rhythmic hyperpolarizations and depolarization of sympathetic ganglion cells induced by caffeine. J Neurophysiol. 1976 May;39(3):547–563. doi: 10.1152/jn.1976.39.3.547. [DOI] [PubMed] [Google Scholar]
  31. Kuba K., Takeshita S. Simulation of intracellular Ca2+ oscillation in a sympathetic neurone. J Theor Biol. 1981 Dec 21;93(4):1009–1031. doi: 10.1016/0022-5193(81)90352-0. [DOI] [PubMed] [Google Scholar]
  32. Li Y. X., Rinzel J., Keizer J., Stojilković S. S. Calcium oscillations in pituitary gonadotrophs: comparison of experiment and theory. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):58–62. doi: 10.1073/pnas.91.1.58. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Lipscombe D., Madison D. V., Poenie M., Reuter H., Tsien R. W., Tsien R. Y. Imaging of cytosolic Ca2+ transients arising from Ca2+ stores and Ca2+ channels in sympathetic neurons. Neuron. 1988 Jul;1(5):355–365. doi: 10.1016/0896-6273(88)90185-7. [DOI] [PubMed] [Google Scholar]
  34. Llano I., DiPolo R., Marty A. Calcium-induced calcium release in cerebellar Purkinje cells. Neuron. 1994 Mar;12(3):663–673. doi: 10.1016/0896-6273(94)90221-6. [DOI] [PubMed] [Google Scholar]
  35. Lytton J., Westlin M., Hanley M. R. Thapsigargin inhibits the sarcoplasmic or endoplasmic reticulum Ca-ATPase family of calcium pumps. J Biol Chem. 1991 Sep 15;266(26):17067–17071. [PubMed] [Google Scholar]
  36. Lückhoff A., Clapham D. E. Inositol 1,3,4,5-tetrakisphosphate activates an endothelial Ca(2+)-permeable channel. Nature. 1992 Jan 23;355(6358):356–358. doi: 10.1038/355356a0. [DOI] [PubMed] [Google Scholar]
  37. McCarron J. G., McGeown J. G., Reardon S., Ikebe M., Fay F. S., Walsh J. V., Jr Calcium-dependent enhancement of calcium current in smooth muscle by calmodulin-dependent protein kinase II. Nature. 1992 May 7;357(6373):74–77. doi: 10.1038/357074a0. [DOI] [PubMed] [Google Scholar]
  38. Meyer T., Stryer L. Molecular model for receptor-stimulated calcium spiking. Proc Natl Acad Sci U S A. 1988 Jul;85(14):5051–5055. doi: 10.1073/pnas.85.14.5051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Mészáros L. G., Bak J., Chu A. Cyclic ADP-ribose as an endogenous regulator of the non-skeletal type ryanodine receptor Ca2+ channel. Nature. 1993 Jul 1;364(6432):76–79. doi: 10.1038/364076a0. [DOI] [PubMed] [Google Scholar]
  40. Nishimura T., Akasu T., Tokimasa T. A slow calcium-dependent chloride current in rhythmic hyperpolarization in neurones of the rabbit vesical pelvic ganglia. J Physiol. 1991 Jun;437:673–690. doi: 10.1113/jphysiol.1991.sp018618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Pfaffinger P. J., Leibowitz M. D., Subers E. M., Nathanson N. M., Almers W., Hille B. Agonists that suppress M-current elicit phosphoinositide turnover and Ca2+ transients, but these events do not explain M-current suppression. Neuron. 1988 Aug;1(6):477–484. doi: 10.1016/0896-6273(88)90178-x. [DOI] [PubMed] [Google Scholar]
  42. Putney J. W., Jr Capacitative calcium entry revisited. Cell Calcium. 1990 Nov-Dec;11(10):611–624. doi: 10.1016/0143-4160(90)90016-n. [DOI] [PubMed] [Google Scholar]
  43. Rooney T. A., Sass E. J., Thomas A. P. Characterization of cytosolic calcium oscillations induced by phenylephrine and vasopressin in single fura-2-loaded hepatocytes. J Biol Chem. 1989 Oct 15;264(29):17131–17141. [PubMed] [Google Scholar]
  44. Rousseau E., Ladine J., Liu Q. Y., Meissner G. Activation of the Ca2+ release channel of skeletal muscle sarcoplasmic reticulum by caffeine and related compounds. Arch Biochem Biophys. 1988 Nov 15;267(1):75–86. doi: 10.1016/0003-9861(88)90010-0. [DOI] [PubMed] [Google Scholar]
  45. Rousseau E., Meissner G. Single cardiac sarcoplasmic reticulum Ca2+-release channel: activation by caffeine. Am J Physiol. 1989 Feb;256(2 Pt 2):H328–H333. doi: 10.1152/ajpheart.1989.256.2.H328. [DOI] [PubMed] [Google Scholar]
  46. Rousseau E., Smith J. S., Meissner G. Ryanodine modifies conductance and gating behavior of single Ca2+ release channel. Am J Physiol. 1987 Sep;253(3 Pt 1):C364–C368. doi: 10.1152/ajpcell.1987.253.3.C364. [DOI] [PubMed] [Google Scholar]
  47. Somogyi R., Stucki J. W. Hormone-induced calcium oscillations in liver cells can be explained by a simple one pool model. J Biol Chem. 1991 Jun 15;266(17):11068–11077. [PubMed] [Google Scholar]
  48. Tepikin A. V., Kostyuk P. G., Snitsarev V. A., Belan P. V. Extrusion of calcium from a single isolated neuron of the snail Helix pomatia. J Membr Biol. 1991 Jul;123(1):43–47. doi: 10.1007/BF01993961. [DOI] [PubMed] [Google Scholar]
  49. Tepikin A. V., Petersen O. H. Mechanisms of cellular calcium oscillations in secretory cells. Biochim Biophys Acta. 1992 Oct 27;1137(2):197–207. doi: 10.1016/0167-4889(92)90202-m. [DOI] [PubMed] [Google Scholar]
  50. Thastrup O., Cullen P. J., Drøbak B. K., Hanley M. R., Dawson A. P. Thapsigargin, a tumor promoter, discharges intracellular Ca2+ stores by specific inhibition of the endoplasmic reticulum Ca2(+)-ATPase. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2466–2470. doi: 10.1073/pnas.87.7.2466. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Tsien R. W., Tsien R. Y. Calcium channels, stores, and oscillations. Annu Rev Cell Biol. 1990;6:715–760. doi: 10.1146/annurev.cb.06.110190.003435. [DOI] [PubMed] [Google Scholar]
  52. Wakui M., Osipchuk Y. V., Petersen O. H. Receptor-activated cytoplasmic Ca2+ spiking mediated by inositol trisphosphate is due to Ca2(+)-induced Ca2+ release. Cell. 1990 Nov 30;63(5):1025–1032. doi: 10.1016/0092-8674(90)90505-9. [DOI] [PubMed] [Google Scholar]
  53. Wimsatt D. K., Hohl C. M., Brierley G. P., Altschuld R. A. Calcium accumulation and release by the sarcoplasmic reticulum of digitonin-lysed adult mammalian ventricular cardiomyocytes. J Biol Chem. 1990 Sep 5;265(25):14849–14857. [PubMed] [Google Scholar]
  54. Woods N. M., Cuthbertson K. S., Cobbold P. H. Repetitive transient rises in cytoplasmic free calcium in hormone-stimulated hepatocytes. Nature. 1986 Feb 13;319(6054):600–602. doi: 10.1038/319600a0. [DOI] [PubMed] [Google Scholar]
  55. Zweifach A., Lewis R. S. Mitogen-regulated Ca2+ current of T lymphocytes is activated by depletion of intracellular Ca2+ stores. Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6295–6299. doi: 10.1073/pnas.90.13.6295. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES