Hostname: page-component-5c6d5d7d68-wtssw Total loading time: 0 Render date: 2024-08-26T16:32:29.615Z Has data issue: false hasContentIssue false
  • English
  • Français

The gap junction blockers carbenoxolone and 18β-glycyrrhetinic acid antagonize cone-driven light responses in the mouse retina

Published online by Cambridge University Press:  18 November 2003

YINGQIU XIA  and
SCOTT NAWY
YINGQIU XIA
Affiliation:
Departments of Ophthalmology and Visual Science, and Neuroscience, Albert Einstein College of Medicine, Bronx
SCOTT NAWY
Affiliation:
Departments of Ophthalmology and Visual Science, and Neuroscience, Albert Einstein College of Medicine, Bronx
Get access Rights & Permissions [Opens in a new window]

Abstract

Gap junctions are widely expressed throughout the retina, and play an important role in the processing of visual information. It has been proposed that horizontal cells express unpaired gap junctions, or hemichannels, in their dendrites, and that current flowing through hemichannels reduces transmembrane voltage at cone terminals, promoting the opening of Ca2+ channels near sites of transmitter release. This model predicts that pharmacological block of gap junctions should reduce the Ca2+ current at the equivalent cone voltage, thereby decreasing the postsynaptic light response. To test this prediction, and estimate the relative magnitude of this effect on third-order cells, we recorded light responses in mouse ganglion cells under photopic conditions and applied two gap junction antagonists, carbenoxolone and the structurally related 18β-glycyrrhetinic acid (GA). Both carbenoxolone and GA decreased the size of the light response to about 30% of control. Cells that were physiologically identified as ON, OFF, or ON/OFF were equally affected by carbenoxolone/GA. These gap junction blockers did not interfere with gamma-aminobutyric acid (GABA) or glutamate receptors, as they did not affect responses to direct activation of these receptors. Under control conditions, spots larger than 200 μm in diameter activated ganglion cell receptive-field surrounds. Comparing responses to small and large spots before and during carbenoxolone treatment, we found that carbenoxolone did not preferentially inhibit surround antagonism at the ganglion cell level, but instead scaled the responses to all spot sizes. Our results extend the findings of studies in lower vertebrates which showed that light responses in horizontal cells are decreased by carbenoxolone treatment, and support the idea that hemichannels in the outer retina, most likely on horizontal cells, constitute important gates that are critical for allowing light responses to move forward into the retinal circuit. Furthermore, it suggests that ganglion cell surrounds are generated in the inner retina.

Keywords

Ganglion cellCarbenoxoloneGap junctionMouse retina
Type
Research Article
Information
Visual Neuroscience , Volume 20 , Issue 4 , July 2003 , pp. 429 - 435
Copyright
2003 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

REFERENCES

Baylor, D.A., Fuortes, M.G., & O'Bryan, P.M. (1971). Receptive fields of cones in the retina of the turtle. Journal of Physiology 214, 265–294.Google Scholar
Bloomfield, S.A., Xin, D., & Persky, S.E. (1995). A comparison of receptive field and tracer coupling size of horizontal cells in the rabbit retina. Visual Neuroscience 12, 985–999.Google Scholar
Brivanlou, I.H., Warland, D.K., & Meister, M. (1998). Mechanisms of concerted firing among retinal ganglion cells. Neuron 20, 527–539.Google Scholar
Cook, P.B. & McReynolds, J.S. (1998). Lateral inhibition in the inner retina is important for spatial tuning of ganglion cells. Nature Neuroscience 1, 714–719.Google Scholar
Deans, M.R. & Paul, D.L. (2001). Mouse horizontal cells do not express connexin26 or connexin36. Cell Communication & Adhesion 8, 361–366.Google Scholar
Deans, M.R., Volgyi, B., Goodenough, D.A., Bloomfield, S.A., & Paul, D.L. (2002). Connexin36 is essential for transmission of rod-mediated visual signals in the mammalian retina. Neuron 36, 703–712.Google Scholar
DeVries, S.H. (2000). Bipolar cells use kainate and AMPA receptors to filter visual information into separate channels. Neuron 28, 847–856.Google Scholar
DeVries, S.H. & Schwartz, E.A. (1989). Modulation of an electrical synapse between solitary pairs of catfish horizontal cells by dopamine and second messengers. Journal of Physiology 414, 351–375.Google Scholar
DeVries, S.H. & Schwartz, E.A. (1992). Hemi-gap-junction channels in solitary horizontal cells of the catfish retina. Journal of Physiology 445, 201–230.Google Scholar
DeVries, S.H. & Schwartz, E.A. (1999). Kainate receptors mediate synaptic transmission between cones and ‘Off’ bipolar cells in a mammalian retina. Nature 397, 157–160.Google Scholar
DeVries, S.H., Qi, X., Smith, R., Makous, W., & Sterling, P. (2002). Electrical Coupling between Mammalian Cones. Current Biology 12, 1900–1907.Google Scholar
Feigenspan, A., Teubner, B., Willecke, K., & Weiler, R. (2001). Expression of neuronal connexin36 in AII amacrine cells of the mammalian retina. Journal of Neuroscience 21, 230–239.Google Scholar
Feigenspan, A., Wassle, H., & Bormann, J. (1993). Pharmacology of GABA receptor Cl− channels in rat retinal bipolar cells. Nature 361, 159–162.Google Scholar
Flores-Herr, N., Protti, D.A., & Wassle, H. (2001). Synaptic currents generating the inhibitory surround of ganglion cells in the mammalian retina. Journal of Neuroscience 21, 4852–4863.Google Scholar
Hidaka, S., Shingai, R., Dowling, J.E., & Naka, K. (1989). Junctions form between catfish horizontal cells in culture. Brain Research 498, 53–63.Google Scholar
Hornstein, E.P., Verweij, J., & Schnapf, J.L. (2002). Absolute sensitivity and functional connectivity of rod/cone coupling in Macaque retina. Society for Neuroscience 28, Program No. 13.13. 2002 Abstract Viewer/Itinerary Planner.Google Scholar
Kamermans, M., Fahrenfort, I., Schultz, K., Janssen-Bienhold, U., Sjoerdsma, T., & Weiler, R. (2001). Hemichannel-mediated inhibition in the outer retina. Science 292, 1178–1180.Google Scholar
Kaneko, A. (1971). Electrical connexions between horizontal cells in the dogfish retina. Journal of Physiology 213, 95–105.Google Scholar
Mangel, S.C. (1991). Analysis of the horizontal cell contribution to the receptive field surround of ganglion cells in the rabbit retina. Journal of Physiology 442, 211–234.Google Scholar
McMahon, M.J., Packer, O., & Dacey, D.M. (2003). Circuitry of the parasol ganglion cell receptive field surround. IOVS 44, E-abstract 3236.Google Scholar
Mills, S.L. & Massey, S.C. (1995). Differential properties of two gap junctional pathways made by AII amacrine cells. Nature 377, 734–737.Google Scholar
Mills, S.L., O'Brien, J.J., Li, W., O'Brien, J., & Massey, S.C. (2001). Rod pathways in the mammalian retina use connexin 36. Journal of Comparative Neurology 436, 336–350.Google Scholar
Molokanova, E., Trivedi, B., Savchenko, A., & Kramer, R.H. (1997). Modulation of rod photoreceptor cyclic nucleotide-gated channels by tyrosine phosphorylation. Journal of Neuroscience 17, 9068–9076.Google Scholar
Naka, K.I. & Rushton, W.A. (1967). The generation and spread of S-potentials in fish (Cyprinidae). Journal of Physiology 192, 437–461.Google Scholar
Naka, K.I. & Witkovsky, P. (1972). Dogfish ganglion cell discharge resulting from extrinsic polarization of the horizontal cells. Journal of Physiology 223, 449–460.Google Scholar
Nakajima, Y., Iwakabe, H., Akazawa, C., Nawa, H., Shigemoto, R., Mizuno, N., & Nakanishi, S. (1993). Molecular characterization of a novel retinal metabotropic glutamate receptor mGluR6 with a high agonist selectivity for L-2-amino-4-phosphonobutyrate. Journal of Biological Chemistry 268, 11868–11873.Google Scholar
Picaud, S., Pattnaik, B., Hicks, D., Forster, V., Fontaine, V., Sahel, J., & Dreyfus, H. (1998). GABAA and GABAC receptors in adult porcine cones: Evidence from a photoreceptor-glia co-culture model. Journal of Physiology 513, 33–42.Google Scholar
Raviola, E. & Gilula, N.B. (1975). Intramembrane organization of specialized contacts in the outer plexiform layer of the retina. A freeze-fracture study in monkeys and rabbits. Journal of Cell Biology 65, 192–222.Google Scholar
Rieke, F. & Schwartz, E.A. (1994). A cGMP-gated current can control exocytosis at cone synapses. Neuron 13, 863–873.Google Scholar
Shields, C.R., Tran, M.N., Wong, R.O., & Lukasiewicz, P.D. (2000). Distinct ionotropic GABA receptors mediate presynaptic and postsynaptic inhibition in retinal bipolar cells. Journal of Neuroscience 20, 2673–2682.Google Scholar
Vaney, D.I., Nelson, J.C., & Pow, D.V. (1998). Neurotransmitter coupling through gap junctions in the retina. Journal of Neuroscience 18, 10594–10602.Google Scholar
Vardi, N. & Sterling, P. (1994). Subcellular localization of GABAA receptor on bipolar cells in macaque and human retina. Vision Research 34, 1235–1246.Google Scholar
Witkovsky, P., Owen, W.G., & Woodworth, M. (1983). Gap junctions among the perikarya, dendrites, and axon terminals of the luminosity-type horizontal cell of the turtle retina. Journal of Comparative Neurology 216, 359–368.Google Scholar
Zhang, D., Pan, Z.H., Zhang, X., Brideau, A.D., & Lipton, S.A. (1995). Cloning of a gamma-aminobutyric acid type C receptor subunit in rat retina with a methionine residue critical for picrotoxinin channel block. Proceedings of the National Academy of Sciences of the U.S.A. 92, 11756–11760.Google Scholar