Skip to main content
PMC home page
The Journal of General Physiology logoLink to The Journal of General Physiology
. 1995 Apr 1;105(4):537–567. doi: 10.1085/jgp.105.4.537

Caffeine- and ryanodine-sensitive Ca(2+)-induced Ca2+ release from the endoplasmic reticulum in honeybee photoreceptors

PMCID: PMC2216935  PMID: 7608657

Abstract

Light stimulation of invertebrate microvillar photoreceptors causes a large rapid elevation in Cai, shown previously to modulate the adaptational state of the cells. Cai rises, at least in part, as a result of Ins(1,4,5)P3-induced Ca2+ release from the submicrovillar endoplasmic reticulum (ER). Here, we provide evidence for Ca(2+)- induced Ca2+ release (CICR) in an insect photoreceptor. In situ microphotometric measurements of Ca2+ fluxes across the ER membrane in permeabilized slices of drone bee retina show that (a) caffeine induces Ca2+ release from the ER; (b) caffeine and Ins(1,4,5)P3 open distinct Ca2+ release pathways because only caffeine-induced Ca2+ release is ryanodine sensitive and heparin insensitive, and because caffeine and Ins(1,4,5)P3 have additive effects on the rate of Ca2+ release; (c) Ca2+ itself stimulates release of Ca2+ via a ryanodine-sensitive pathway; and (d) cADPR is ineffective in releasing Ca2+. Microfluorometric intracellular Ca2+ measurements with fluo-3 indicate that caffeine induces a persistent elevation in Cai. Electrophysiological recordings demonstrate that caffeine mimics all aspects of Ca(2+)-mediated facilitation and adaptation in drone photoreceptors. We conclude that the ER in drone photoreceptors contains, in addition to the Ins(1,4,5)P3-sensitive release pathway, a CICR pathway that meets key pharmacological criteria for a ryanodine receptor. Coexpression of both release mechanisms could be required for the production of rapid light-induced Ca2+ elevations, because Ca2+ amplifies its own release through both pathways by a positive feedback. CICR may also mediate the spatial spread of Ca2+ release from the submicrovillar ER toward more remote ER subregions, thereby activating Ca(2+)-sensitive cell processes that are not directly involved in phototransduction.

Full Text

The Full Text of this article is available as a PDF (1.7 MB).

Selected References

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

  1. Anderson K., Lai F. A., Liu Q. Y., Rousseau E., Erickson H. P., Meissner G. Structural and functional characterization of the purified cardiac ryanodine receptor-Ca2+ release channel complex. J Biol Chem. 1989 Jan 15;264(2):1329–1335. [PubMed] [Google Scholar]
  2. Bader C., Baumann F., Bertrand D. Role of intracellular calcium and sodium in light adaptation in the retina of the honey bee drone (Apis mellifera, L). J Gen Physiol. 1976 Apr;67(4):475–491. doi: 10.1085/jgp.67.4.475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baumann O., Walz B., Somlyo A. V., Somlyo A. P. Electron probe microanalysis of calcium release and magnesium uptake by endoplasmic reticulum in bee photoreceptors. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):741–744. doi: 10.1073/pnas.88.3.741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Beil F. U., von Chak D., Hasselbach W., Weber H. H. Competition between oxalate and phosphate during active calcium accumulation by sarcoplasmic vesicles. Z Naturforsch C. 1977 Mar-Apr;32(3-4):281–287. doi: 10.1515/znc-1977-3-421. [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. Bertrand D., Fuortes G., Muri R. Pigment transformation and electrical responses in retinula cells of drone, Apis mellifera male. J Physiol. 1979 Nov;296:431–441. doi: 10.1113/jphysiol.1979.sp013014. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. 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]
  8. Brown J. E., Blinks J. R. Changes in intracellular free calcium concentration during illumination of invertebrate photoreceptors. Detection with aequorin. J Gen Physiol. 1974 Dec;64(6):643–665. doi: 10.1085/jgp.64.6.643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Brown J. E., Brown P. K., Pinto L. H. Detection of light-induced changes of intracellular ionized calcium concentration in Limulus ventral photoreceptors using arsenazo III. J Physiol. 1977 May;267(2):299–320. doi: 10.1113/jphysiol.1977.sp011814. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Brown J. E., Rubin L. J., Ghalayini A. J., Tarver A. P., Irvine R. F., Berridge M. J., Anderson R. E. myo-Inositol polyphosphate may be a messenger for visual excitation in Limulus photoreceptors. Nature. 1984 Sep 13;311(5982):160–163. doi: 10.1038/311160a0. [DOI] [PubMed] [Google Scholar]
  11. Capovilla M., Cervetto L., Torre V. The effect of phosphodiesterase inhibitors on the electrical activity of toad rods. J Physiol. 1983 Oct;343:277–294. doi: 10.1113/jphysiol.1983.sp014892. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Coles J. A., Orkand R. K. Modification of potassium movement through the retina of the drone (Apis mellifera male) by glial uptake. J Physiol. 1983 Jul;340:157–174. doi: 10.1113/jphysiol.1983.sp014756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Corson D. W., Fein A., Schmidt J. Two effects of phosphodiesterase inhibitors on Limulus ventral photoreceptors. Brain Res. 1979 Nov 2;176(2):365–368. doi: 10.1016/0006-8993(79)90990-9. [DOI] [PubMed] [Google Scholar]
  14. Demaurex N., Lew D. P., Krause K. H. Cyclopiazonic acid depletes intracellular Ca2+ stores and activates an influx pathway for divalent cations in HL-60 cells. J Biol Chem. 1992 Feb 5;267(4):2318–2324. [PubMed] [Google Scholar]
  15. Fein A., Lisman J. Localized desensitization of Limulus photoreceptors produced by light or intracellular calcium ion injection. Science. 1975 Mar 21;187(4181):1094–1096. doi: 10.1126/science.1114339. [DOI] [PubMed] [Google Scholar]
  16. Fein A., Payne R., Corson D. W., Berridge M. J., Irvine R. F. Photoreceptor excitation and adaptation by inositol 1,4,5-trisphosphate. Nature. 1984 Sep 13;311(5982):157–160. doi: 10.1038/311157a0. [DOI] [PubMed] [Google Scholar]
  17. Fein A., Tsacopoulos M. Activation of mitochondrial oxidative metabolism by calcium ions in Limulus ventral photoreceptor. Nature. 1988 Feb 4;331(6155):437–440. doi: 10.1038/331437a0. [DOI] [PubMed] [Google Scholar]
  18. Feng J. J., Carson J. H., Morgan F., Walz B., Fein A. Three-dimensional organization of endoplasmic reticulum in the ventral photoreceptors of Limulus. J Comp Neurol. 1994 Mar 8;341(2):172–183. doi: 10.1002/cne.903410204. [DOI] [PubMed] [Google Scholar]
  19. 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]
  20. Fleischer S., Ogunbunmi E. M., Dixon M. C., Fleer E. A. Localization of Ca2+ release channels with ryanodine in junctional terminal cisternae of sarcoplasmic reticulum of fast skeletal muscle. Proc Natl Acad Sci U S A. 1985 Nov;82(21):7256–7259. doi: 10.1073/pnas.82.21.7256. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Galione A., Lee H. C., Busa W. B. Ca(2+)-induced Ca2+ release in sea urchin egg homogenates: modulation by cyclic ADP-ribose. Science. 1991 Sep 6;253(5024):1143–1146. doi: 10.1126/science.1909457. [DOI] [PubMed] [Google Scholar]
  23. Galione A., White A., Willmott N., Turner M., Potter B. V., Watson S. P. cGMP mobilizes intracellular Ca2+ in sea urchin eggs by stimulating cyclic ADP-ribose synthesis. Nature. 1993 Sep 30;365(6445):456–459. doi: 10.1038/365456a0. [DOI] [PubMed] [Google Scholar]
  24. Ganitkevich V. Y., Isenberg G. Contribution of Ca(2+)-induced Ca2+ release to the [Ca2+]i transients in myocytes from guinea-pig urinary bladder. J Physiol. 1992 Dec;458:119–137. doi: 10.1113/jphysiol.1992.sp019409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. HAGINS W. A., ZONANA H. V., ADAMS R. G. Local membrane current in the outer segments of squid photoreceptors. Nature. 1962 Jun 2;194:844–847. doi: 10.1038/194844a0. [DOI] [PubMed] [Google Scholar]
  26. Hardie R. C., Minke B. The trp gene is essential for a light-activated Ca2+ channel in Drosophila photoreceptors. Neuron. 1992 Apr;8(4):643–651. doi: 10.1016/0896-6273(92)90086-s. [DOI] [PubMed] [Google Scholar]
  27. Hardie R. C. Phototransduction. The invertebrate enigma. Nature. 1993 Nov 11;366(6451):113–114. doi: 10.1038/366113a0. [DOI] [PubMed] [Google Scholar]
  28. Hasan G., Rosbash M. Drosophila homologs of two mammalian intracellular Ca(2+)-release channels: identification and expression patterns of the inositol 1,4,5-triphosphate and the ryanodine receptor genes. Development. 1992 Dec;116(4):967–975. doi: 10.1242/dev.116.4.967. [DOI] [PubMed] [Google Scholar]
  29. Hill T. D., Berggren P. O., Boynton A. L. Heparin inhibits inositol trisphosphate-induced calcium release from permeabilized rat liver cells. Biochem Biophys Res Commun. 1987 Dec 31;149(3):897–901. doi: 10.1016/0006-291x(87)90492-x. [DOI] [PubMed] [Google Scholar]
  30. Imagawa T., Smith J. S., Coronado R., Campbell K. P. Purified ryanodine receptor from skeletal muscle sarcoplasmic reticulum is the Ca2+-permeable pore of the calcium release channel. J Biol Chem. 1987 Dec 5;262(34):16636–16643. [PubMed] [Google Scholar]
  31. Inui M., Saito A., Fleischer S. Purification of the ryanodine receptor and identity with feet structures of junctional terminal cisternae of sarcoplasmic reticulum from fast skeletal muscle. J Biol Chem. 1987 Feb 5;262(4):1740–1747. [PubMed] [Google Scholar]
  32. Kobayashi S., Somlyo A. V., Somlyo A. P. Heparin inhibits the inositol 1,4,5-trisphosphate-dependent, but not the independent, calcium release induced by guanine nucleotide in vascular smooth muscle. Biochem Biophys Res Commun. 1988 Jun 16;153(2):625–631. doi: 10.1016/s0006-291x(88)81141-0. [DOI] [PubMed] [Google Scholar]
  33. Koshiyama H., Lee H. C., Tashjian A. H., Jr Novel mechanism of intracellular calcium release in pituitary cells. J Biol Chem. 1991 Sep 15;266(26):16985–16988. [PubMed] [Google Scholar]
  34. Lai F. A., Erickson H. P., Rousseau E., Liu Q. Y., Meissner G. Purification and reconstitution of the calcium release channel from skeletal muscle. Nature. 1988 Jan 28;331(6154):315–319. doi: 10.1038/331315a0. [DOI] [PubMed] [Google Scholar]
  35. Lee H. C., Aarhus R., Graeff R., Gurnack M. E., Walseth T. F. Cyclic ADP ribose activation of the ryanodine receptor is mediated by calmodulin. Nature. 1994 Jul 28;370(6487):307–309. doi: 10.1038/370307a0. [DOI] [PubMed] [Google Scholar]
  36. Lee H. C., Aarhus R., Walseth T. F. Calcium mobilization by dual receptors during fertilization of sea urchin eggs. Science. 1993 Jul 16;261(5119):352–355. doi: 10.1126/science.8392749. [DOI] [PubMed] [Google Scholar]
  37. Levy S., Fein A. Relationship between light sensitivity and intracellular free Ca concentration in Limulus ventral photoreceptors. A quantitative study using Ca-selective microelectrodes. J Gen Physiol. 1985 Jun;85(6):805–841. doi: 10.1085/jgp.85.6.805. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Lisman J. E., Brown J. E. Effects of intracellular injection of calcium buffers on light adaptation in Limulus ventral photoreceptors. J Gen Physiol. 1975 Oct;66(4):489–506. doi: 10.1085/jgp.66.4.489. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Lisman J. E., Brown J. E. The effects of intracellular iontophoretic injection of calcium and sodium ions on the light response of Limulus ventral photoreceptors. J Gen Physiol. 1972 Jun;59(6):701–719. doi: 10.1085/jgp.59.6.701. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Maaz G., Stieve H. The correlation of the receptor potential with the light induced transient increase in intracellular calcium-concentration measured by absorption change of arsenazo III injected into Limulus ventral nerve photoreceptor cell. Biophys Struct Mech. 1980;6(3):191–208. doi: 10.1007/BF00537293. [DOI] [PubMed] [Google Scholar]
  41. Mason M. J., Garcia-Rodriguez C., Grinstein S. Coupling between intracellular Ca2+ stores and the Ca2+ permeability of the plasma membrane. Comparison of the effects of thapsigargin, 2,5-di-(tert-butyl)-1,4-hydroquinone, and cyclopiazonic acid in rat thymic lymphocytes. J Biol Chem. 1991 Nov 5;266(31):20856–20862. [PubMed] [Google Scholar]
  42. McNulty T. J., Taylor C. W. Caffeine-stimulated Ca2+ release from the intracellular stores of hepatocytes is not mediated by ryanodine receptors. Biochem J. 1993 May 1;291(Pt 3):799–801. doi: 10.1042/bj2910799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  43. McPherson P. S., Campbell K. P. Characterization of the major brain form of the ryanodine receptor/Ca2+ release channel. J Biol Chem. 1993 Sep 15;268(26):19785–19790. [PubMed] [Google Scholar]
  44. McPherson P. S., Campbell K. P. Solubilization and biochemical characterization of the high affinity [3H]ryanodine receptor from rabbit brain membranes. J Biol Chem. 1990 Oct 25;265(30):18454–18460. [PubMed] [Google Scholar]
  45. McPherson P. S., Campbell K. P. The ryanodine receptor/Ca2+ release channel. J Biol Chem. 1993 Jul 5;268(19):13765–13768. [PubMed] [Google Scholar]
  46. McPherson P. S., Kim Y. K., Valdivia H., Knudson C. M., Takekura H., Franzini-Armstrong C., Coronado R., Campbell K. P. The brain ryanodine receptor: a caffeine-sensitive calcium release channel. Neuron. 1991 Jul;7(1):17–25. doi: 10.1016/0896-6273(91)90070-g. [DOI] [PubMed] [Google Scholar]
  47. Meissner G. Ryanodine activation and inhibition of the Ca2+ release channel of sarcoplasmic reticulum. J Biol Chem. 1986 May 15;261(14):6300–6306. [PubMed] [Google Scholar]
  48. Miki N., Keirns J. J., Marcus F. R., Freeman J., Bitensky M. W. Regulation of cyclic nucleotide concentrations in photoreceptors: an ATP-dependent stimulation of cyclic nucleotide phosphodiesterase by light. Proc Natl Acad Sci U S A. 1973 Dec;70(12):3820–3824. doi: 10.1073/pnas.70.12.3820. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Minke B., Selinger Z. The inositol-lipid pathway is necessary for light excitation in fly photoreceptors. Soc Gen Physiol Ser. 1992;47:201–217. [PubMed] [Google Scholar]
  50. Minke B., Tsacopoulos M. Light induced sodium dependent accumulation of calcium and potassium in the extracellular space of bee retina. Vision Res. 1986;26(5):679–690. doi: 10.1016/0042-6989(86)90082-9. [DOI] [PubMed] [Google Scholar]
  51. 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]
  52. Nori A., Villa A., Podini P., Witcher D. R., Volpe P. Intracellular Ca2+ stores of rat cerebellum: heterogeneity within and distinction from endoplasmic reticulum. Biochem J. 1993 Apr 1;291(Pt 1):199–204. doi: 10.1042/bj2910199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Payne R., Fein A. Inositol 1,4,5 trisphosphate releases calcium from specialized sites within Limulus photoreceptors. J Cell Biol. 1987 Apr;104(4):933–937. doi: 10.1083/jcb.104.4.933. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. Payne R., Fein A. Localized adaptation within the rhabdomeral lobe of Limulus ventral photoreceptors. J Gen Physiol. 1983 May;81(5):767–769. doi: 10.1085/jgp.81.5.767. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Payne R., Flores T. M., Fein A. Feedback inhibition by calcium limits the release of calcium by inositol trisphosphate in Limulus ventral photoreceptors. Neuron. 1990 Apr;4(4):547–555. doi: 10.1016/0896-6273(90)90112-s. [DOI] [PubMed] [Google Scholar]
  56. Payne R., Potter B. V. Injection of inositol trisphosphorothioate into Limulus ventral photoreceptors causes oscillations of free cytosolic calcium. J Gen Physiol. 1991 Jun;97(6):1165–1186. doi: 10.1085/jgp.97.6.1165. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Payne R., Walz B., Levy S., Fein A. The localization of calcium release by inositol trisphosphate in Limulus photoreceptors and its control by negative feedback. Philos Trans R Soc Lond B Biol Sci. 1988 Jul 26;320(1199):359–379. doi: 10.1098/rstb.1988.0082. [DOI] [PubMed] [Google Scholar]
  58. Phillips A. M., Bull A., Kelly L. E. Identification of a Drosophila gene encoding a calmodulin-binding protein with homology to the trp phototransduction gene. Neuron. 1992 Apr;8(4):631–642. doi: 10.1016/0896-6273(92)90085-r. [DOI] [PubMed] [Google Scholar]
  59. Putney J. W., Jr A model for receptor-regulated calcium entry. Cell Calcium. 1986 Feb;7(1):1–12. doi: 10.1016/0143-4160(86)90026-6. [DOI] [PubMed] [Google Scholar]
  60. Ranganathan R., Harris G. L., Stevens C. F., Zuker C. S. A Drosophila mutant defective in extracellular calcium-dependent photoreceptor deactivation and rapid desensitization. Nature. 1991 Nov 21;354(6350):230–232. doi: 10.1038/354230a0. [DOI] [PubMed] [Google Scholar]
  61. Saito A., Inui M., Radermacher M., Frank J., Fleischer S. Ultrastructure of the calcium release channel of sarcoplasmic reticulum. J Cell Biol. 1988 Jul;107(1):211–219. doi: 10.1083/jcb.107.1.211. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Seidler N. W., Jona I., Vegh M., Martonosi A. Cyclopiazonic acid is a specific inhibitor of the Ca2+-ATPase of sarcoplasmic reticulum. J Biol Chem. 1989 Oct 25;264(30):17816–17823. [PubMed] [Google Scholar]
  63. Sitsapesan R., McGarry S. J., Williams A. J. Cyclic ADP-ribose competes with ATP for the adenine nucleotide binding site on the cardiac ryanodine receptor Ca(2+)-release channel. Circ Res. 1994 Sep;75(3):596–600. doi: 10.1161/01.res.75.3.596. [DOI] [PubMed] [Google Scholar]
  64. Stieve H., Benner S. The light-induced rise in cytosolic calcium starts later than the receptor current of the Limulus ventral photoreceptor. Vision Res. 1992 Mar;32(3):403–416. doi: 10.1016/0042-6989(92)90232-8. [DOI] [PubMed] [Google Scholar]
  65. Taylor C. W., Marshall I. C. Calcium and inositol 1,4,5-trisphosphate receptors: a complex relationship. Trends Biochem Sci. 1992 Oct;17(10):403–407. doi: 10.1016/0968-0004(92)90009-x. [DOI] [PubMed] [Google Scholar]
  66. 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]
  67. Walz B., Baumann O. Calcium-sequestering cell organelles: in situ localization, morphological and functional characterization. Prog Histochem Cytochem. 1989;20(2):1–47. doi: 10.1016/s0079-6336(89)80005-1. [DOI] [PubMed] [Google Scholar]
  68. Walz B. Ca2+-sequestering smooth endoplasmic reticulum in an invertebrate photoreceptor. I. Intracellular topography as revealed by OsFeCN staining and in situ Ca accumulation. J Cell Biol. 1982 Jun;93(3):839–848. doi: 10.1083/jcb.93.3.839. [DOI] [PMC free article] [PubMed] [Google Scholar]
  69. Walz B. Ca2+-sequestering smooth endoplasmic reticulum in an invertebrate photoreceptor. II. Its properties as revealed by microphotometric measurements. J Cell Biol. 1982 Jun;93(3):849–859. doi: 10.1083/jcb.93.3.849. [DOI] [PMC free article] [PubMed] [Google Scholar]
  70. Walz B. Enhancement of sensitivity in photoreceptors of the honey been drone by light and by Ca2+. J Comp Physiol A. 1992 Jun;170(5):605–613. doi: 10.1007/BF00199336. [DOI] [PubMed] [Google Scholar]
  71. Walz B. Subcellular calcium localization and AT0-dependent Ca2+-uptake by smooth endoplasmic reticulum in an invertebrate photoreceptor cell. An ultrastrucutral, cytochemical and X-ray microanalytical study. Eur J Cell Biol. 1979 Oct;20(1):83–91. [PubMed] [Google Scholar]
  72. White A. M., Watson S. P., Galione A. Cyclic ADP-ribose-induced Ca2+ release from rat brain microsomes. FEBS Lett. 1993 Mar 8;318(3):259–263. doi: 10.1016/0014-5793(93)80524-x. [DOI] [PubMed] [Google Scholar]
  73. Worley P. F., Baraban J. M., Supattapone S., Wilson V. S., Snyder S. H. Characterization of inositol trisphosphate receptor binding in brain. Regulation by pH and calcium. J Biol Chem. 1987 Sep 5;262(25):12132–12136. [PubMed] [Google Scholar]

Articles from The Journal of General Physiology are provided here courtesy of The Rockefeller University Press

RESOURCES