Skip to main content
Log in

Ca2+ signalling and membrane current activated by cADPr in starfish oocytes

  • Cell and Molecular Physiology
  • Published:
Pflügers Archiv Aims and scope Submit manuscript

Abstract

Cyclic ADP-ribose (cADPr) is a second messenger that regulates intracellular free [Ca2+] ([Ca2+]i) in a variety of cell types, including immature oocytes from the starfish Astropecten auranciacus. In this study, we employed confocal laser scanning microscopy and voltage clamp techniques to investigate the source of the cADPr-elicited Ca2+ wave originating from the cortical Ca2+ patches we have described previously. The Ca2+ swing was accompanied by a membrane current with a reversal potential of ≈+20 mV. Decreasing external Na+ almost abolished the current without affecting the Ca2+ response. Removal of extracellular Ca2+ altered neither the Ca2+ transient nor the ionic current, nor did the holding potential exert any effect on the Ca2+ wave. Both the Ca2+ response and the membrane current were abolished when BAPTA, ruthenium red or 8-NH2-cADPr were preinjected into the oocytes, while perfusion with ADPr did not elicit any [Ca2+]i increase or ionic current. However, elevating [Ca2+]i by uncaging Ca2+ from nitrophenyl- (NP-EGTA) or by photoliberating inositol 1,4,5-trisphosphate (InsP3) induced an ionic current with biophysical properties similar to that elicited by cADPr. These results suggest that cADPr activates a Ca2+ wave by releasing Ca2+ from intracellular ryanodine receptors and that the rise in [Ca2+]i triggers a non-selective monovalent cation current that does not seem to contribute to the global Ca2+ elevation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1A–C.
Fig. 2A, B.
Fig. 3A, B.
Fig. 4A–D.
Fig. 5A–C.
Fig. 6A–D.
Fig. 7A–D.

Similar content being viewed by others

References

  1. Albrieux M, Sardet C, Villaz M (1997) The two intracellular Ca2+ release channels, ryanodine receptor and inositol 1,4,5-trisphosphate receptor, play different roles during fertilization in ascidians. Dev Biol 189:74–185

    Article  Google Scholar 

  2. Albrieux M, Lee HC, Villaz M (1998) Calcium signaling by cyclic ADP-ribose, NAADP, and inositol trisphosphate are involved in distinct functions in ascidian oocytes. J Biol Chem 273:14566–14574

    Article  CAS  PubMed  Google Scholar 

  3. Albrieux M, Moutin MJ, Grunwald D, Villaz M (2000) Calmodulin and immunophilin are required as functional partners of a ryanodine receptor in ascidian oocytes at fertilization. Dev Biol 225:101–111

    Article  CAS  PubMed  Google Scholar 

  4. Ashby MC, Craske M, Park MK, Gerasimenko OV, Burgoyne RD, Petersen OH, Tepikin AV (2002) Localized Ca2+ uncaging reveals polarized distribution of Ca2+-sensitive Ca2+ release sites: mechanism of unidirectional Ca2+ waves. J Cell Biol 158:283–292

    Article  CAS  PubMed  Google Scholar 

  5. Berridge G, Dickinson G, Parrington J, Galione A, Patel S (2002) Solubilization of receptors for the novel Ca2+-mobilizing messenger, nicotinic acid adenine dinucleotide phosphate. J Biol Chem 277:43717–43723

    Article  CAS  Google Scholar 

  6. Borra MT, O'Neill FJ, Jackson MD, Marshall B, Verdin E, Foltz KR, Denu JM (2002) Conserved enzymatic production and biological effect of O-acetyl-ADP-ribose by silent information regulator 2-like NAD+-dependent deacetylasesJ Biol Chem 277:12632–12641

    Google Scholar 

  7. Cancela JM, Churchill GC, Galione A (1999) Coordination of agonist-induced Ca2+-signalling patterns by NAADP in pancreatic acinar cells. Nature 398:74–76

    Article  CAS  PubMed  Google Scholar 

  8. Cancela JM, Gerasimenko OV, Gerasimenko JV, Tepikin AV, Petersen OH (2000) Two different but converging messenger pathways to intracellular Ca2+ release: the roles of nicotinic acid adenine dinucleotide phosphate, cyclic ADP-ribose and inositol trisphosphate. EMBO J 19:2549–2557

    CAS  PubMed  Google Scholar 

  9. Cancela JM, Van Coppenolle F, Galione A, Tepikin AV, Petersen OH (2002) Transformation of local Ca2+ spikes to global Ca2+ transients: the combinatorial roles of multiple Ca2+ releasing messengers. EMBO J 21:909–919

    Article  CAS  PubMed  Google Scholar 

  10. Carafoli E, Santella L, Branca D, Brini M (2001) Generation, control, and processing of cellular calcium signals. Crit Rev Biochem Mol Biol 36:107–260

    CAS  PubMed  Google Scholar 

  11. Churchill GC, Galione A (2001) NAADP induces Ca2+ oscillations via a two-pool mechanism by priming IP3- and cADPR-sensitive Ca2+ stores. EMBO J 20:2666–2671

    Article  CAS  PubMed  Google Scholar 

  12. Crawford JH, Wootton JF, Seabrook GR, Scott RH (1997) Activation of Ca2+-dependent currents in dorsal root ganglion neurons by metabotropic glutamate receptors and cyclic ADP-ribose precursors. J Neurophysiol 77:2573–2584

    CAS  PubMed  Google Scholar 

  13. Currie KP, Swann K, Galione A, Scott RH (1992) Activation of Ca2+-dependent currents in cultured rat dorsal root ganglion neurones by a sperm factor and cyclic ADP-ribose. Mol Biol Cell 3:1415–1425

    CAS  PubMed  Google Scholar 

  14. Giovannucci DR, Bruce JI, Straub SV, Arreola J, Sneyd J, Shuttleworth TJ, Yule DI (2002) Cytosolic Ca2+ and Ca2+-activated Cl current dynamics: insights from two functionally distinct mouse exocrine cells. J Physiol (Lond) 540:469–484

    Google Scholar 

  15. Guia A, Wan X, Courtemanche M, Leblanc N (1999) Local Ca2+ entry through L-type Ca2+ channels activates Ca2+-dependent K+ channels in rabbit coronary myocytes. Circ Res 84:1032–1042

    CAS  PubMed  Google Scholar 

  16. Guo X, Becker PL (1997) Cyclic ADP-ribose-gated Ca2+ release in sea urchin eggs requires an elevated [Ca2+]. J Biol Chem 272:16984–16989

    Article  CAS  PubMed  Google Scholar 

  17. Guse AH (2002) Cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP): novel regulators of Ca2+-signaling and cell function. Curr Mol Med 2:273–282

    CAS  PubMed  Google Scholar 

  18. Guse AH, Berg I, da Silva CP, Potter BV, Mayr GW (1997) Ca2+ entry induced by cyclic ADP-ribose in intact T-lymphocytes. J Biol Chem 272:8546–8550

    CAS  PubMed  Google Scholar 

  19. Guse AH, da Silva CP, Berg I, Skapenko AL, Weber K, Heyer P, Hohenegger M, Ashamu GA, Schulze-Koops H, Potter BV, Mayr GW (1999) Regulation of calcium signalling in T lymphocytes by the second messenger cyclic ADP-ribose. Nature 398:70–73

    Google Scholar 

  20. Hagiwara S, Yoshii M (1979) Effects of internal potassium and sodium on the anomalous rectification of the starfish egg as examined by internal perfusion. J Physiol (Lond) 292:251–265

    Google Scholar 

  21. Hille B (1992) Ionic channels of excitable membranes, 2nd Edn., Sinauer, Sunderland

  22. Ito K, Miyashita Y, Kasai H (1999) Kinetic control of multiple forms of Ca2+ spikes by inositol trisphosphate in pancreatic acinar cells. J Cell Biol 146:405–413

    Article  CAS  PubMed  Google Scholar 

  23. Kidd JF, Thorn P (2000) Intracellular Ca2+ and Cl channel activation in secretory cells. Annu Rev Physiol 62:493–513

    CAS  PubMed  Google Scholar 

  24. Kidd JF, Fogarty KE, Tuft RA, Thorn P (1999) The role of Ca2+ feedback in shaping InsP3-evoked Ca2+ signals in mouse pancreatic acinar cells. J Physiol (Lond) 520:187–201

    Google Scholar 

  25. Kiselyov K, Shin DM, Shcheynikov N, Kurosaki T, Muallem S (2001) Regulation of Ca2+-release-activated Ca2+ current (Icrac) by ryanodine receptors in inositol 1,4,5-trisphosphate-receptor-deficient DT40 cells. Biochem J 360:17–22

    Article  CAS  PubMed  Google Scholar 

  26. Kockskamper J, Sheehan KA, Bare DJ, Lipsius SL, Mignery GA, Blatter LA (2001) Activation and propagation of Ca2+ release during excitation-contraction coupling in atrial myocytes. Biophys J 81:2590–2605

    CAS  PubMed  Google Scholar 

  27. Krause E, Gobel A, Schulz I (2002) Cell side-specific sensitivities of intracellular Ca2+ stores for inositol 1,4,5-trisphosphate, cyclic ADP-ribose, and nicotinic acid adenine dinucleotide phosphate in permeabilized pancreatic acinar cells from mouse. J Biol Chem 277:11696–11702

    Article  CAS  PubMed  Google Scholar 

  28. Lansman JB (1983) Voltage-clamp study of the conductance activated at fertilization in the starfish egg. J Physiol (Lond) 345:353–372

    Google Scholar 

  29. Lansman JB (1987) Calcium current and calcium-activated inward current in the oocyte of the starfish Leptasterias hexactis. J Physiol (Lond) 390:397–413

    Google Scholar 

  30. Lee HC (2001) Physiological functions of cyclic ADP-ribose and NAADP as calcium messengers. Annu Rev Pharmacol Toxicol 41:317–45

    Google Scholar 

  31. Lim D, Kyozuka K, Gragnaniello G, Carafoli E, Santella L (2001) NAADP+ initiates the Ca2+ response during fertilization of starfish oocytes. FASEB J 15:2257–2267

    Article  CAS  PubMed  Google Scholar 

  32. Mackenzie L, Bootman MD, Berridge MJ, Lipp P (2001) The role of inositol 1,4,5-trisphosphate receptors in Ca2+ signalling and the generation of arrhythmias in rat atrial myocytes. J Physiol (Lond) 530:417–429

    Google Scholar 

  33. Maruyama Y, Petersen OH (1982) Cholecystokinin activation of single-channel currents is mediated by internal messenger in pancreatic acinar cells. Nature 300:61–63

    CAS  PubMed  Google Scholar 

  34. Meszaros LG, Bak J, Chu A (1993) Cyclic ADP-ribose as an endogenous regulator of the non-skeletal type ryanodine receptor Ca2+ channel. Nature 364:76–79

    Google Scholar 

  35. Miyazaki SI, Ohmori H, Sasaki S (1975) Action potential and non-linear current-voltage relation in starfish oocytes. J Physiol (Lond) 246:37–54

    Google Scholar 

  36. Miyazaki SI, Ohmori H, Sasaki S (1975) Potassium rectifications of the starfish oocyte membrane and their changes during oocyte maturation. J Physiol (Lond) 246:55–78

    Google Scholar 

  37. Moody WJ, Bosma MM (1985) Hormone-induced loss of surface membrane during maturation of starfish oocytes: differential effects on potassium and calcium channels. Dev Biol 112:396–404

    CAS  PubMed  Google Scholar 

  38. Moody WJ, Lansman JB (1983) Developmental regulation of Ca2+ and K+ currents during hormone-induced maturation of starfish oocytes. Proc Natl Acad Sci U S A 80:3096–3100

    CAS  PubMed  Google Scholar 

  39. Morikawa H, Khodakhah K, Williams JT (2003) Two intracellular pathways mediate metabotropic glutamate receptor-induced Ca2+ mobilization in dopamine neurons. J Neurosci 23:149–157

    CAS  PubMed  Google Scholar 

  40. Nusco GA, Lim D, Sabala P, Santella L (2002) Ca2+ response to cADPr during maturation and fertilization of starfish oocytes. Biochem Biophys Res Commun 290:1015–1021

    Article  CAS  PubMed  Google Scholar 

  41. Park MK, Lomax RB, Tepikin AV, Petersen OH (2001) Local uncaging of caged Ca2+ reveals distribution of Ca2+-activated Cl channels in pancreatic acinar cells. Proc Natl Acad Sci USA 98:10948–10953

    CAS  PubMed  Google Scholar 

  42. Pollock J, Crawford JH, Wootton JF, Seabrook GR, Scott RH (1999) Metabotropic glutamate receptor activation and intracellular cyclic ADP-ribose release Ca2+ from the same store in cultured DRG neurones. Cell Calcium 26:139–148

    Article  CAS  PubMed  Google Scholar 

  43. Rusinko N, Lee HC (1989) Widespread occurrence in animal tissues of an enzyme catalyzing the conversion of NAD+ into a cyclic metabolite with intracellular Ca2+-mobilizing activity. J Biol Chem 264:11725–11731

    CAS  PubMed  Google Scholar 

  44. Ryan JS, Baldridge WH, Kelly ME (1999) Purinergic regulation of cation conductances and intracellular Ca2+ in cultured rat retinal pigment epithelial cells. J Physiol (Lond) 520:745–759

    Google Scholar 

  45. Santella L, Kyozuka K (1997) Effects of 1-methyladenine on nuclear Ca2+ transients and meiosis resumption in starfish oocytes are mimicked by the nuclear injection of inositol 1,4,5-trisphosphate and cADP-ribose. Cell Calcium 22:11–20

    CAS  PubMed  Google Scholar 

  46. Santella L, De Riso L, Gragnaniello G, Kyozuka K (1999) Cortical granule translocation during maturation of starfish oocytes requires cytoskeletal rearrangement triggered by InsP3-mediated Ca2+ release. Exp Cell Res 248:567–574

    Article  CAS  PubMed  Google Scholar 

  47. Santella L, Kyozuka K, Genazzani AA, De Riso L, Carafoli E (2000) Nicotinic acid adenine dinucleotide phosphate-induced Ca2+ release. Interactions among distinct Ca2+ mobilizing mechanisms in starfish oocytes. J Biol Chem 275:8301–8306

    Article  CAS  PubMed  Google Scholar 

  48. Santella L, Nusco GA, Lim D (2002) Cyclic ADP-ribose and NAADP. Structures, metabolism and functions. Kluwer, Norwell

  49. Santella L, Ercolano E, Nusco GA, Lim D, Moccia F (2003) Activated M-phase-promoting factor (MPF) is exported from the nucleus of starfish oocytes to increase the sensitivity of the Ins(1,4,5)P3 receptors. Biochem Soc Trans 31:79–82

    CAS  PubMed  Google Scholar 

  50. Simoncini L, Moody WJ (1990) Changes in voltage-dependent currents and membrane area during maturation of starfish oocytes: species differences and similarities. Dev Biol 138:194–201

    CAS  PubMed  Google Scholar 

  51. Sitsapesan R, Williams AJ (1995) Cyclic ADP-ribose and related compounds activate sheep skeletal sarcoplasmic reticulum Ca2+ release channel. Am J Physiol 268:C1235–C1240

    CAS  PubMed  Google Scholar 

  52. Stricker SA, Centonze VE, Melendez RF (1994) Calcium dynamics during starfish oocyte maturation and fertilization. Dev. Biol. 166:34–58

    Google Scholar 

  53. Thomas D, Mason MJ, Mahaut-Smith MP (2002) Depolarisation-evoked Ca2+ waves in the non-excitable rat megakaryocyte. J Physiol (Lond) 537:371–378

    Google Scholar 

  54. Thomas JM, Summerhill RJ, Fruen BR, Churchill GC, Galione A (2002) Calmodulin Dissociation mediates desensitization of the cADPR-induced Ca2+ release mechanism. Curr Biol 12:2018–2022

    Article  CAS  PubMed  Google Scholar 

  55. Wilding M, Russo GL, Galione A, Marino M, Dale B (1998) ADP-ribose gates the fertilization channel in ascidian oocytes. Am J Physiol 275:C1277–C1283

    CAS  PubMed  Google Scholar 

  56. Yang J, McBride S, Mak DO, Vardi N, Palczewski K, Haeseleer F, Foskett JK (2002) Identification of a family of calcium sensors as protein ligands of inositol trisphosphate receptor Ca2+ release channels. Proc Natl Acad Sci U S A 99:7711–7716

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Drs. E. Carafoli and F. Tanzi for critical reading of the manuscript. The help of the Marine Resources Service of the Stazione Zoologica for maintaining the starfish is also gratefully acknowledged.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to L. Santella.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Moccia, F., Nusco, G.A., Lim, D. et al. Ca2+ signalling and membrane current activated by cADPr in starfish oocytes. Pflugers Arch - Eur J Physiol 446, 541–552 (2003). https://doi.org/10.1007/s00424-003-1076-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-003-1076-1

Keywords

Navigation