Modulation of Connexon Density in Gap Junctions of Fish Horizontal Cells

  • Hartwig Wolburg
  • Gertrud Kurz-Isler
Part of the Neuroscience Intelligence Unit book series (NIU.LANDES)


Gap junctions in the vertebrate retina are among those most widely investigated in the central nervous system. Many methods have been applied to measure receptive field sizes of retinal neurons in order to estimate the activity and strength of interneuronal coupling or to describe the morphology of the underlying gap junctions. In this chapter, the results gotten by application of the freeze-fracture method to problems of gap junctional modulation in the retina will be summarized. The advantage of this method is the two-dimensional visualization of planar lipidic monolayers of membranes showing inserted particles or—as in gap junctions—connexons. In conventional ultrathin section electron microscopy, gap junctions are linear domains with variable lengths; their ultrastructural peculiarities such as size, shape or the arrangement of connexons cannot be recognized. However, using standard freeze-fracture techniques the linkage of the gap junctional domain with underlying cytoskeletal elements cannot be observed. Surprisingly, the observation of cytoplasmic surfaces in the area of gap junctions as described, for example, in liver,1 cardiac2 and lens gap junctions3 was not performed in gap junctions of the retina.


Amacrine Cell Horizontal Cell Optic Nerve Crush Vertebrate Retina Receptive Field Size 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Hirokawa N, Heuser J. The inside and outside of gap junction membranes visualized by deep etching. Cell 1982; 30: 395–406.PubMedCrossRefGoogle Scholar
  2. 2.
    Shibata Y, Yamamoto T. Cytoplasmic surface ultrastructures of cardiac gap junctions as revealed by quick-freeze, deep-etch replicas. Anat Record 1986; 214: 107–12.CrossRefGoogle Scholar
  3. 3.
    Hatae T, Iida H, Kuraoka A et al. Cytplasmic surface ultrastructures of gap junctions in bovine lens fibers. Invest Ophthalmol Vis Sci 1993; 34: 2164–73.PubMedGoogle Scholar
  4. 4.
    Wolburg H, Rohlmann A. Structure-function relationships in gap junctions. Int Rev Cytol 1995; 157: 315–73.PubMedCrossRefGoogle Scholar
  5. 5.
    Wolburg H, Kurz-Isler G. Dynamics of gap junctions between horizontal cells in the goldfish retina. Exp Brain Res 1985; 60: 397–401.PubMedCrossRefGoogle Scholar
  6. 6.
    Raviola E, Gilula NB. Gap junctions between photoreceptor cells in the vertebrate retina. Proc Natl Acad Sci USA 1973; 70: 1677–81.PubMedCrossRefGoogle Scholar
  7. 7.
    Copenhagen DR, Owen WG. Coupling between rod photoreceptors in a vertebrate retina. Nature 1976; 260: 57–59.PubMedCrossRefGoogle Scholar
  8. 8.
    Tsukamoto Y, Masarachia P, Schein SJ et al. Gap junctions between the pedicles of macaque foveal cones. Vis Res 1992; 32: 1809–15.PubMedCrossRefGoogle Scholar
  9. 9.
    Dacheux RF, Raviola E. Horizontal cells in the retina of the rabbit. J Neurosci 1982; 2: 1486–93.PubMedGoogle Scholar
  10. 10.
    Bloomfield SA, Miller RF. A physiological and morphological study of the horizontal cell types of the rabbit retina. J Comp Neurol 1982; 208: 288–303.PubMedCrossRefGoogle Scholar
  11. 11.
    Vaney DI. The coupling pattern of axon-bearing horizontal cells in the mammalian retina. Proc R Soc Lond B 1993; 252: 93–101.CrossRefGoogle Scholar
  12. 12.
    Kujiraoka T, Saito T. Electrical coupling between bipolar cells in the carp retina. Proc Nat! Acad Sci USA 1986; 83: 4063–66.CrossRefGoogle Scholar
  13. 13.
    Saito T, Kujiraoka T. Characteristics of bipolar-bipolar coupling in the carp retina. J Gen Physiol 1988; 91: 275–87.PubMedCrossRefGoogle Scholar
  14. 14.
    Umino O, Maehara M, Hidaka S et al. Electrical coupling between bipolar cells in the retina. Invest Ophthalmol Vis Sci 1993; 34: 984.Google Scholar
  15. 15.
    Bloomfield SA. Relationship between receptive and dendritic field size of amacrine cells in the rabbit retina. J Neurophysiol 1992; 68: 711–25.PubMedGoogle Scholar
  16. 16.
    Hampson ECGM, Vaney DI, Weiler R. Dopaminergic modulation of gap junction permeability between amacrine cells in mammalian retina. J Neurosci 1992; 12: 4911–22.PubMedGoogle Scholar
  17. 17.
    Hidaka S, Maehara M, Umino O et al. Lateral gap junction connections between retinal amacrine cells summating sustained responses. NeuroReport 1993; 5: 29–32.PubMedCrossRefGoogle Scholar
  18. 18.
    Hitchcock PF. Neurobiotin coupling between developing ganglion cells in the retina of the goldfish. Invest Ophthalmol Vis Sci 1993; 34: 878.Google Scholar
  19. 19.
    Vaney DI. Many diverse types of retinal neurons show tracer coupling when injected with biocytin or neurobiotin. Neurosci Lett 1991; 125: 187–90.PubMedCrossRefGoogle Scholar
  20. 20.
    Vaney DI. Patterns of neuronal coupling in the retina. Progr Ret Eye Res 1994; 13: 301–55.CrossRefGoogle Scholar
  21. 21.
    Uga S, Smelser GK. Comparative study of the fine structure of retinal Müller cells in various vertebrates. Invest Ophthalmol 1973; 12: 434–48.PubMedGoogle Scholar
  22. 22.
    Burns MS, Tyler NK. Interglial cell gap junctions increase in urethane-induced photoreceptor degeneration in rats. Invest Ophthalmol Vis Sci 1990; 31: 1690–1701.PubMedGoogle Scholar
  23. 23.
    Wolburg H, Reichelt, W, Stolzenburg J-U et al. Rabbit retinal Müller cells in cell culture show gap and tight junctions which they do not express in situ. Neurosci Lett 1990; 111: 58–63.PubMedCrossRefGoogle Scholar
  24. 24.
    Holländer H, Makarov F, Dreher Z et al. Structure of the macroglia of the retina: sharing and division of labour between astrocytes and Müller cells. J Comp Neurol 1991; 313: 587–603.PubMedCrossRefGoogle Scholar
  25. 25.
    Robinson SR, Hampson ECGM, Munro MN et al. Unidirectional coupling of gap junctions between neuroglia. Science 1993; 262: 1072–74.PubMedCrossRefGoogle Scholar
  26. 26.
    Dowling JE, Boycott BB. Organization of the primate retina: electron microscopy. Proc R Soc Lond B 1966; 166: 80–111.PubMedCrossRefGoogle Scholar
  27. 27.
    Murakami M, Miyachi E-I, Takahashi K-I. Modulation of gap junctions between horizontal cells by second messengers. Progr Ret Eye Res 1995; 14: 197–221.CrossRefGoogle Scholar
  28. 28.
    Dixon JS, Cronly-Dillon JR. The fine structure of the developing retina in Xenopus laevis. J Embryol Exp Morph 1972; 28: 659–66.PubMedGoogle Scholar
  29. 29.
    Fusisawa H, Morioka H, Watanabe K et al. A decay of gap junctions in association with cell differentiation of neural retina in chick embryonic development. J Cell Sci 1976; 2 2: 585–96.Google Scholar
  30. 30.
    Hayes BP. The distribution of intercellular gap junctions in the developing retina and pigment epithelium of Xenopus laevis. Anat Embryol 1976; 150: 99–111.PubMedGoogle Scholar
  31. 31.
    Hayes BP. Intercellular gap junctions in the developing retina and pigment epithelium of the chick. Anat Embryol 1977; 151: 325–34.PubMedCrossRefGoogle Scholar
  32. 32.
    Vardi N, Hertzberg E, Sterling P. Gap junction distribution in cat and monkey retina visualized with monoclonal antibody to connexin32. Soc Neurosci Abstr 1990; 16: 1076.Google Scholar
  33. 33.
    Jones CR, Becker DL, Cook JE. Gap junctions in the rat retina: immunoreactivity with antisera raised to oligopeptides of connexins Cx32 and Cx43. Neurosci Letters 1992; Suppl 42: S34.Google Scholar
  34. 34.
    Janssen-Bienhold U, Schöpe B, BuschmannGebhardt B, Dermietzel R, Weiler R. Identification of neuronal connexin proteins in the retina. In: Elsner N, Menzel R, ed. Proc 23rd Göttingen Neurobiol Conf. Stuttgart, New York: Georg Thieme Verlag, 1995: 458.Google Scholar
  35. 35.
    Naka K-I, Rushton WAH. The generation and spread of S-potentials in fish (Cyprinidae). J Physiol 1967; 192: 437–61.PubMedGoogle Scholar
  36. 36.
    Kaneko A. Electrical connexins between horizontal cells in the dogfish retina. J Physiol 1971; 213: 95–105.PubMedGoogle Scholar
  37. 37.
    Kaneko A, Stuart AE. Coupling between horizontal cells in the carp retina revealed by diffusion of lucifer yellow. Neurosci Lett 1984; 47: 1–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Piccolino M, Neyton J, Witkovsky P et al. Gamma-aminobutyric acaid antagonists decrease junctional communication between horizontal cells of the retina. Proc Natl Acad Sci USA 1982; 79: 3671–75.PubMedCrossRefGoogle Scholar
  39. 39.
    Teranishi T, Negishi K, Kato S. Regulatory effect of dopamine on spatial properties of horizontal cells in carp retina. J Neurosci 1984; 4: 1271–80.PubMedGoogle Scholar
  40. 40.
    Marc RE, Liu WLS, Muller JF. Gap junctions in the inner plexiform layer of the goldfish retina. Vision Res 1988; 28: 9–24.PubMedGoogle Scholar
  41. 41.
    Goddard JC, Behrens UD, Wagner HJ, Djamgoz MBA. Biocytin: intracellular staining, dye-coupling and immunocytochemistry in carp retina. Neuro Report 1991; 2: 755–58.Google Scholar
  42. 42.
    Cuenca N, Fernandez E, Garcia M, De Juan J. Dendrites of rod dominant ON-bipolar cells are coupled by gap junctions in carp retina. Neurosci Lett 1993; 162: 34–38.PubMedCrossRefGoogle Scholar
  43. 43.
    Teranishi T, Negishi K. Double-staining of horizontal and amacrine cells by intracellular injection with Lucifer Yellow and biocytin in carp retina. Neuroscience 1994; 59: 217–26.PubMedCrossRefGoogle Scholar
  44. 44.
    Lasansky A. Interactions between horizontal cells of the salamander retina. Invest Ophthalmol 1976; 15: 909–16.Google Scholar
  45. 45.
    Raviola E. Intercellular junctions in the outer plexiform layer of the retina. Invest Ophthalmol Vis Sci 1976; 15: 881–95.Google Scholar
  46. 46.
    Raviola E, Gilula NB. Intramembrane organization of specialized contacts in the outer plexiform layer of the retina. J Cell Biol 1975; 65: 192–222.PubMedCrossRefGoogle Scholar
  47. 47.
    Cooper NGF, Mc Laughlin BJ. Gap junctions in the outer plexiform layer of the chick retina: Thin section and freeze-fracture studies. J Neurocytol 1981; 10: 515–29.PubMedCrossRefGoogle Scholar
  48. 48.
    Zimmerman RP. Bar synapses and gap junc tions in the inner plexiform layer: synaptic relationships of the interstitial amacrine cell of the retina of the cichlid fish, Astronotus ocellatus. J Comp Neurol 1983; 218: 471–79.PubMedCrossRefGoogle Scholar
  49. 49.
    Witkovsky P, Owen WG, Woodworth M. Gap junctions among the perikarya, dendrites, and axon terminals of the luminosity-type horizontal cell of the turtle retina. J Comp Neurol 1983; 261: 359–68.CrossRefGoogle Scholar
  50. 50.
    Tonosaki A, Washioka H, Nakamura H et al. Complementary freeze-fracture replication: an example of its use in the study of horizontal cell gap junctions of the carp retina. J Electr Microsc Tech 1985; 2: 187–92.CrossRefGoogle Scholar
  51. 51.
    Kouyama N, Watanabe K. Gap junctional contacts of luminosity-type horizontal cells in the carp retina. A novel pathway of signal conduction from the cell body to the axon terminal. J Comp Neurol 1986; 249: 404–10.PubMedCrossRefGoogle Scholar
  52. 52.
    Marshal(DW, Dowling JE. Synapses of cone horizontal cell axons in goldfish retina. J Comp Neurol 1987; 256: 430–43.Google Scholar
  53. 53.
    Kamermans M, van Dijk BW, Spekreijse H. Interaction between the soma and the axon terminal of horizontal cells in carp retina. Vision Res 1990; 30: 1011–16.PubMedCrossRefGoogle Scholar
  54. 54.
    Kurz-Isler G, Voigt T, Wolburg H. Modulation of connexon densities in gap junctions of horizontal cell perikarya and axon terminals in fish retina: effects of light/dark cycles, interruption of the optic nerve and application of dopamine. Cell Tiss Res 1992; 268: 267–75.CrossRefGoogle Scholar
  55. 55.
    Piccolino M, Neyton J, Gerschenfeld HM. Decrease of of the gap junction permeability induced by dopamine and cyclic 3’-5° adenosine-monophosphate in horizontal cells of the turtle retina. J Neurosci 1984; 4: 2477–88.PubMedGoogle Scholar
  56. 56.
    Piccolino M, Demontis G, Witkovsky P et al. Involvement of D1 and D2 dopamine receptors in the control of horizontal cell electrical coupling in the turtle retina. Europ. J Neurosci 1989; 1: 247–57.CrossRefGoogle Scholar
  57. 57.
    McMahon DG, Knapp AG, Dowling JE. Horizontal cell gap junctions: single channel conductance and modulation by dopamine. Proc Natl Acad Sci USA 1989; 86: 7639–43.PubMedCrossRefGoogle Scholar
  58. 58.
    Zucker CL, Dowling JE. Centrifugal fibers synapse on dopaminergic interplexiform cells in the teleost retina. Nature 1987; 300: 166–68.CrossRefGoogle Scholar
  59. 59.
    Negishi K, Teranishi T, Kato S. A GABA antagonist, bicuculline, exerts its uncoupling action on external horizontal cells through dopamine cells in carp retina. Neurosci Lett 1983; 37: 261–66.PubMedCrossRefGoogle Scholar
  60. 60.
    Piccolino M, Witkovsky P, Trimarchi C. Dopaminergic mechanisms underlying the reduction of electrical coupling between horizontal cells of the turtle retina induced by d-amphetamine, bicuculline, and veratri-dine. J Neurosci 1987; 7: 2273–84.PubMedGoogle Scholar
  61. 61.
    Lasater EM. Retinal horizontal cell gap junctional conductance is modulated by dopamine through a cyclic AMP-dependent protein kinase. Proc Natl Acad Sci USA 1987; 84: 7319–23.PubMedCrossRefGoogle Scholar
  62. 62.
    Lasater EM, Dowling JE. Dopamine decreases conductance of the electrical junctions between cultured retinal horizontal cells. Proc Natl Acad Sci USA 1985; 82: 3025–29.PubMedCrossRefGoogle Scholar
  63. 63.
    Laufer M, Salas R, Medina R et al. Cyclic adenosine monophosphate as a second messenger in horizontal cell uncoupling in the teleost retina. J Neurosci Res 1989; 24: 299–310.PubMedCrossRefGoogle Scholar
  64. 64.
    Kurz-Iller G, Wolburg H. Gap junctions between horizontal cells in the cyprinid fish alter rapidly their structure during light and dark adaptation. Neurosci Lett 1986; 67: 7–12.CrossRefGoogle Scholar
  65. 65.
    Kurz-Islet G, Wolburg H. Light-dependent dynamics of gap junctions between horizontal cells in the retina of the crucian carp. Cell Tiss Res 1988; 251: 641–49.CrossRefGoogle Scholar
  66. 66.
    Baldridge WH, Ball AK, Miller RG. Dopaminergic regulation of horizontal cell gap junction particle density in goldfish retina. J Comp Neurol 1987; 265: 428–36.PubMedCrossRefGoogle Scholar
  67. 67.
    Baldridge WH, Ball AK, Miller RG. Gap junction particle density of horizontal cells in goldfish retinas lesioned with 6-OHDA. J Comp Neurol 1989; 287: 238–46.PubMedCrossRefGoogle Scholar
  68. 68.
    Weiler R Kohler K, Kolbinger W et al. Dopaminergic neuromodulation in the retina of lower vertebrates. Neurosci Res 1988; Suppl 8: S183–96.Google Scholar
  69. 69.
    Schmitz Y, Wolburg H. Gap junction morphology of retinal horizontal cells is sensitive to pH alterations in vitro. Cell Tiss Res 1991; 263: 303–10.CrossRefGoogle Scholar
  70. 70.
    Vaughan DK, Lasater EM. Distribution of F-actin in bipolar and horizontal cells of bass retinas. Am J Physiol 1990; 259: C205–14.PubMedGoogle Scholar
  71. 71.
    Hidaka S, Shingai R, Dowling JE et al. Junctions form between catfish horizontal cells in culture. Brain Res 1989; 498: 53–63.PubMedCrossRefGoogle Scholar
  72. 72.
    Negishi K, Teranishi T, Kato S. Opposite effects of ammonia and carbon dioxide on dye coupling between horizontal cells in the carp retina. Brain Res 1985; 342: 330–39.PubMedCrossRefGoogle Scholar
  73. 73.
    DeVries SH, Schwartz EA. Modulation of an electrical synapse between solitary pairs of catfish horizontal cells by dopamine and second messengers. J Physiol (Lond) 1989; 414: 351–75.Google Scholar
  74. 74.
    Qian H, Malchow RP, Ripps H. Gap-junctional properties of electrically coupled skate horizontal cells in culture. Vis Neurosci 1993; 10: 287–95.PubMedCrossRefGoogle Scholar
  75. 75.
    Hampson ECGM, Weiler R, Vaney DI. pH-gated dopaminergic modulation of horizontal cell gap junctions in mammalian retina. Proc R Soc Lond B 1994; 255: 67–72.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1996

Authors and Affiliations

  • Hartwig Wolburg
  • Gertrud Kurz-Isler

There are no affiliations available

Personalised recommendations