Hostname: page-component-78c5997874-g7gxr Total loading time: 0 Render date: 2024-11-17T05:18:48.218Z Has data issue: false hasContentIssue false
  • English
  • Français

Contributions of GABAA receptors and GABAC receptors to acetylcholine release and directional selectivity in the rabbit retina

Published online by Cambridge University Press:  02 June 2009

Stephen C. Massey ,
David M. Linn ,
Christopher A. Kittila  and
Wajid Mirza
Stephen C. Massey
Affiliation:
Department of Ophthalmology and Visual Science, University of Texas Medical School, Houston
David M. Linn
Affiliation:
LSU Eye Center and Neuroscience Center, LSU Medical School, New Orleans
Christopher A. Kittila
Affiliation:
Department of Ophthalmology and Visual Science, University of Texas Medical School, Houston
Wajid Mirza
Affiliation:
Department of Ophthalmology and Visual Science, University of Texas Medical School, Houston
Get access Rights & Permissions [Opens in a new window]

Abstract

GABA is a major inhibitory neurotransmitter in the mammalian retina and it acts at many different sites via a variety of postsynaptic receptors. These include GABAA receptors and bicuculline-resistant GABAC receptors. The release of acetylcholine (ACh) is inhibited by GABA and strongly potentiated by GABA antagonists. In addition, GABA appears to mediate the null inhibition which is responsible for the mechanism of directional selectivity in certain ganglion cells. We have used these two well-known examples of GABA inhibition to compare three GABA antagonists and assess the contributions of GABAA and GABAC receptors. All three GABA antagonists stimulated ACh release by as much as ten-fold. By this measure, the ED50s for SR-95531, bicuculline, and picrotoxin were 0.8, 7.0, and 14 μM, respectively. Muscimol, a potent GABAA agonist, blocked the effects of SR-95531 and bicuculline, but not picrotoxin. This indicates that SR-95531 and bicuculline are competitive antagonists at the GABAA receptor, while picrotoxin blocks GABAA responses by acting at a different, nonreceptor site such as the chloride channel. In the presence of a saturating dose of SR-95531 to completely block GABAA receptors, picrotoxin caused a further increase in the release of ACh. This indicates that picrotoxin potentiates ACh release by a mechanism in addition to the block of GABAA responses, possibly by also blocking GABAC receptors, which have been associated with bipolar cells. All three GABA antagonists abolished directionally selective responses from ON/OFF directional-selective (DS) ganglion cells. In this system, the ED50s for SR-95531, bicuculline, and picrotoxin were 0.7 μM, 8 μM, and 94.6 μM, respectively. The results with SR-95531 and bicuculline indicate that GABAA receptors mediate the inhibition responsible for directional selectivity. The addition of picrotoxin to a high dose of SR-95531 caused no further increase in firing rate. The comparatively high dose required for picrotoxin also suggests that GABAC receptors do not contribute to directional selectivity. This in turn suggests that feedforward GABAA inhibition, as opposed to feedback at bipolar terminals, is responsible for the null inhibition underlying directional selectivity.

Keywords

RetinaGABAACh releaseDirectional selectivitySR-95531BicucullinePicrotoxin
Type
Research Articles
Information
Visual Neuroscience , Volume 14 , Issue 5 , September 1997 , pp. 939 - 948
Copyright
Copyright © Cambridge University Press 1997

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

Ames, A. & Nesbett, F.B. (1981). In vitro retina as an experimental model of the central nervous system. Journal of Neurochemistry 37, 867–877.CrossRefGoogle ScholarPubMed
Ariel, M. & Daw, N.W. (1982). Pharmacological analysis of directionally sensitive rabbit retinal ganglion cells. Journal of Physiology (London) 178, 477–504.Google Scholar
Arnt, J. & Krogsgaard-Larsen, P. (1979). GABA agonists and potential antagonists related to muscimol. Brain Research 177, 395–400.CrossRefGoogle ScholarPubMed
Barker, J.L., McBurney, R.N. & Mathers, D.A. (1983). Convulsant-induced depression of amino acid responses in mouse culture spinal neurones studied under voltage clamp. British Journal of Pharmacology 80, 619–630.CrossRefGoogle ScholarPubMed
Barlow, H.B. & Levick, W.R. (1965). The mechanism of directionally selective units in rabbit's retina. Journal of Physiology (London) 178, 477–504.CrossRefGoogle ScholarPubMed
Beutler, J.A., Karbon, E.W., Brubaker, A.N., Malik, R., Curtis, D.R. & Enna, S.J. (1985). Securinine alkaloids: A new class of GABA receptor antagonist. Brain Research 330, 135–140.CrossRefGoogle ScholarPubMed
Bormann, J. (1988). Electrophysiology of GABAA and GABAb receptor subtypes. Trends in Neuroscience 11, 112–116.CrossRefGoogle ScholarPubMed
Bormann, J. & Feigenspan, A. (1995). GABAC receptors. Trends in Neuroscience 18, 515–519.CrossRefGoogle ScholarPubMed
Brandstätter, J.H., Greferath, U., Euler, T. & Wässle, H. (1995). Co-stratification of GABAA receptors with the directionally selective circuitry of the rat retina. Visual Neuroscience 12, 345–358.CrossRefGoogle ScholarPubMed
Brecha, N., Johnson, D., Peichl, L. & Wässle, H. (1988). Cholinergic amacrine cells of the rabbit retina contain glutamate decarboxylase and gamma-aminobutyrate immunoreactivity. Proceedings of the National Academy of Sciences of the U.S.A. 85, 6187–6191.CrossRefGoogle ScholarPubMed
Caldwell, J.H., Daw, N.W. & Wyatt, H.J. (1978). Effects of picrotoxin and strychnine on rabbit retinal ganglion cells: Lateral interactions for cells with more complex receptive fields. Journal of Physiology (London) 276, 277–298.CrossRefGoogle ScholarPubMed
Chambon, J.P., Feltz, P., Heaulme, M., Restle, S., Schlichter, R., Biziere, K. & Wermuth, C.G. (1985). An arylaminopyridazine derivative of γ-aminobutyric acid (GABA) is a selective and competitive antagonist at the GABA-A receptor site. Proceedings of the National Academy of Sciences of the U.S.A. 82, 1832–1836.CrossRefGoogle ScholarPubMed
Cunningham, J.R. & Neal, M.J. (1983). Effect of γ-aminobutyric acid agonists, glycine, taurine and neuropeptides on acetylcholine release from the rabbit retina. Journal of Physiology (London) 362, 51–67.CrossRefGoogle Scholar
Curtis, D.R., Duggan, A.W., Felix, D. & Johnston, G.A.R. (1971). Bicuculline, an antagonist of GABA and synaptic inhibition in the spinal cord of the cat. Brain Research 32, 69–96.CrossRefGoogle ScholarPubMed
Curtis, D.R. & Malik, R. (1985). Glycine antagonism by RU 5135. European Journal of Pharmacology 110, 383–384.CrossRefGoogle ScholarPubMed
Cutting G.R., Lu, L., O'Hara, B.F., Kasch, L.M., Montrose-Rafizadeh, C., Donovan, D.M., Shimada, S., Antonarakis, S.E., Guggino, W.B. & Uhl, G.R. (1991). Cloning of the gamma-aminobutyric acid (GABA) rho 1 cDNA: A GABA receptor subunit highly expressed in the retina. Proceedings of the National Academy of Sciences of the U.S.A. 88, 2673–2677.Google Scholar
Desarmenien, M., Desaulles, E., Feltz, P. & Hamann, M. (1987). Electrophysiological study of SR 42641, a novel aminopyridazine derivative of GABA: Antagonist properties and receptor selectivity of GABAA versus GABAb responses. British Journal of Pharmacology 90, 287–298.CrossRefGoogle ScholarPubMed
Enz, R., Brändstatter, J.H., Wässle, H. & Bormann, J. (1996). Immunocytochemical localization of the GABAC receptor p subunits in the mammalian retina. Journal of Neuroscience 16, 4479–4490.CrossRefGoogle Scholar
Famiglietti, E.V. (1983 a). On and Off pathways through amacrine cells in mammalian retina: The synaptic connections of ‘starburst’ amacrine cells. Vision Research 23, 1265–1279.CrossRefGoogle ScholarPubMed
Famiglietti, E.V. (1983 b). ‘Starburst’ amacrine cells and cholinergic neurons: Mirror-symmetric ON and OFF amacrine cells of rabbit retina. Brain Research 261, 138–144.CrossRefGoogle ScholarPubMed
Feigenspan, A. & Bormann, J. (1994). Differential pharmacology of GABAA and GABAC receptors on rat retinal bipolar cells. European Journal of Pharmacology 288, 97–104.CrossRefGoogle ScholarPubMed
Feienspan, A., Wä, H. & Bormann, J. (1993). Pharmacology of ABA receptor Cl− channels in rat retinal bipolar cells. Nature 361, 159–162.CrossRefGoogle Scholar
Fritschy, J.M. & Mohler, H. (1995). GABAA-receptor heterogeneity in the adult rat brain: Differential regional and cellular distribution of seven major subunits. Journal of Comparative Neurology 359, 154–94.CrossRefGoogle ScholarPubMed
Gahwiler, B.H., Maurer, R. & Wuthrich, H.J. (1984). Pitrazepin, a novel GABAa antagonist. Neuroscience Letters 45, 311–316.CrossRefGoogle ScholarPubMed
Gillette, M.A. & Dacheux, R.F. (1995). GABA-and glycine-activated currents in the rod bipolar cell of the rabbit retina. Journal of Neurophysiology 74, 856–875.CrossRefGoogle ScholarPubMed
Greferath, U., Müller, F., Wässle, H., Shivers, B. & Seeburg, P. (1994 a). Localization of GABAa receptors in the rat retina. Visual Neuroscience 10, 551–561.CrossRefGoogle Scholar
Greferath, U., Grünert, U., Müller, F. & Wässle, H. (1994 b). Localization of GABAA receptors in the rabbit retina. Cell Tissue Research 276, 295–307.Google ScholarPubMed
Heaulme, M., Chambon, J.P., Leyris, R., Molimard, J.C., Wermuth, C.G. & Biziere, K. (1986). Biochemical characterization of the interaction of three pyridazinyl-GABA derivatives with the GABA-A receptor site. Brain Research 384, 224–231.CrossRefGoogle ScholarPubMed
Heaulme, M., Chambon, J.P., Leyris, R., Wermuth, C.G. & Biziere, K. (1987). Characterization of the binding of [3H]SR 95531, a GABAA antagonist, to rat brain membranes. Journal of Neurochemistry 48, 1677–1686.CrossRefGoogle ScholarPubMed
Kaneko, A., Suzuki, S., Pinto, L.H. & Tachibana, M. (1991). Membrane currents and pharmacology of retinal bipolar cells: A comparative study on goldfish and mouse. Comparative Biochemistry and Physiology 98c, 115–127.Google ScholarPubMed
Kittila, C.A. & Massey, S.C. (1995 a). Effect of ON pathway blockade on directional selectivity in the rabbit retina. Journal of Neurophysiology 73, 703–712.CrossRefGoogle Scholar
Kittila, C.A. & Massey, S.C. (1995 b). Directionally selective retinal ganglion cells show sensitivity to glutamate under cholinergic blockade. Investigative Ophthalmology and Visual Science (Suppl.) 36, S865.Google Scholar
Kittila, C.A. & Massey, S.C. (1997). The pharmacology of directionally selective ganglion cells in the rabbit retina. Journal of Neurophysiology (in press).CrossRefGoogle ScholarPubMed
Krogsgaard-Larsen, P.T., Honore, T. & Thyssen, K. (1978). GABA receptor agonists: Design and structure-activity studies. In GABA-Neurotransmitters, ed. Krogsgaard-Larsen, P., Scheel-Kruger, J. & Kofod, J., pp. 201–216. New York: Academic Press.Google Scholar
Krogsgaard-Larsen, P., Hjeds, H., Curtis, D.R., Leah, J.D. & Peet, M.J. (1982). Glycine antagonists structurally related to muscimol, THIP, or isoguvacine. Journal of Neurochemistry 39, 1319–1324.CrossRefGoogle ScholarPubMed
Linn, D.M., Blazynski, C., Redburn, D.A. & Massey, S.C. (1991). Acetylcholine release from the rabbit retina mediated by kainate receptors. Journal of Neuroscience 11, 111–122.CrossRefGoogle ScholarPubMed
Linn, D.M. & Massey, S.C. (1991). Acetylcholine release from the rabbit retina mediated by NMDA receptors. Journal of Neuroscience 11, 123–133.CrossRefGoogle ScholarPubMed
Linn, D.M. & Massey, S.C. (1992). GABA-mediated inhibition of ACh release from the rabbit retina: A direct effect or bipolar cell feedback? Visual Neuroscience 8, 97–106.CrossRefGoogle ScholarPubMed
Lukasiewicz, P.D., Maple, B.R. & Werblin, F.S. (1994). A novel GABA receptor on bipolar cell terminals in the tiger salamander retina. Journal of Neuroscience 14, 1202–1212.CrossRefGoogle ScholarPubMed
Lukasiewicz, P.D. & Werblin, F.S. (1994). A novel GABA receptor modulaters synaptic transmission from bipolar to ganglion and amacrine cells in the tiger salamander retina. Journal of Neuroscience 14, 1213–1223.CrossRefGoogle Scholar
Lukasiewicz, P.D. & Wong, R.O.L. (1996). The properties of GABAC receptors on ferret retinal bipolar cells. Investigative Ophthalmology and Visual Science (Suppl.) 37, S418.Google Scholar
Macdonald, R.L. & Olsen, R.W. (1994). GABAA receptor channels. Annual Review of Neuroscience 17, 569–602.CrossRefGoogle ScholarPubMed
Marc, R.L., Stell, W.K., Bok, D. & Lam, D.M. (1978). GABA-ergic pathways in the goldfish retina. Journal of Comparative Neurology 182, 221–245.CrossRefGoogle ScholarPubMed
Masland, R.H. & Mills, J.W. (1979). Autoradiographic identification of acetylcholine in the rabbit retina. Journal of Cell Biology 83, 159–178.CrossRefGoogle ScholarPubMed
Masland, R.H., Mills, J.W. & Hayden, S.A. (1984). Acetylcholine-synthesizing amacrine cells: Identification and selective staining by using autoradiography and fluorescent markers. Proceedings of the Royal Society B (London) 223, 79–100.Google ScholarPubMed
Massey, S.C. & Neal, M.J. (1979). The light-evoked release of acetylcholine from the rabbit retina in vivo and its inhibition by GABA. Journal of Neurochemistry 32, 1327–1329.CrossRefGoogle Scholar
Massey, S.C. & Redburn, D.A. (1982). A tonic γ-aminobutyric acid-mediated inhibition of cholinergic amacrine cells in rabbit retina. Journal of Neuroscience 2, 1633–1643.CrossRefGoogle ScholarPubMed
Massey, S.C. & Redburn, D.A. (1987). Transmitter circuits in the vertebrate retina. Progress in Neurobiology 28, 55–96.CrossRefGoogle ScholarPubMed
McCabe, R.T., Wamsley, J.K., Yezuita, J.P. & Olsen, R.W. (1988). A novel GABAa antagonist [3H]SR 95531: Microscopic analysis of binding in the rat brain and allosteric modulation by several benzodiazepine and barbiturate receptor ligands. Synapse 2, 163–173.CrossRefGoogle ScholarPubMed
Michaud, J.C., Mienville, J.M., Chambon, J.P. & Biziere, K. (1986). Interactions between three pyridazinyl-GABA derivatives and central GABA and glycine receptors in the rat, an in vivo microiontophoretic study. Neuropharmacology 25, 1197–1203.CrossRefGoogle ScholarPubMed
Miller, R.F., Zalutsky, R.A. & Massey, S.C. (1986). A perfused rabbit retina preparation suitable for pharmacological studies. Journal of Neuroscience Methods 16, 309–322.CrossRefGoogle ScholarPubMed
Olsen, R.W. (1984). γ-Aminobutyric acid receptor binding antagonism by the amidine steroid RU 5135. European Journal of Pharmacology 103, 333.CrossRefGoogle Scholar
Qian, H. & Dowling, J.E. (1993). Novel GABA responses from rod-driven retinal horizontal cells. Nature 361, 162–164.CrossRefGoogle ScholarPubMed
Qian, H. & Dowling, J.E. (1994). Pharmacology of novel GABA receptors found on rod horizontal cells of the white perch retina. Journal of Neuroscience 14, 4299–4307.CrossRefGoogle ScholarPubMed
Sieghart, W. (1995). Structure and pharmacology of γ-aminobutyric acidA receptor subtypes. Pharmacological Reviews 47, 181–234.Google ScholarPubMed
Simmonds, M.A. (1980). Evidence that bicuculline and picrotoxin act at separate sites to antagonize γ-aminobutyric acid in rat cuneate nucleus. Neuropharmacology 19, 39–45.CrossRefGoogle ScholarPubMed
Ticku, M.K., Ban, M. & Olsen, R.W. (1978). Binding of 3H-alpha-dihydropicrotoxinin, a gamma-aminobutyric acid synaptic antagonist, to rat brain membrane. Molecular Pharmacology 14, 391–402.Google Scholar
Wermuth, C.G. & Biziere, K. (1986). Pyridazinyl-GABA derivatives: A new class of synthetic GABAA antagonists. Trends in Pharmacological Sciences 7, 421–424.CrossRefGoogle Scholar
Worms, I. (1979). Neuropharmacological spectrum of muscimol. Life Science 25, 607–636.CrossRefGoogle ScholarPubMed
Wyatt, H.J. & Daw, N.W. (1976). Specific effect of neurotransmitter antagonists on ganglion cells in rabbit retina. Science 191, 204–205.CrossRefGoogle ScholarPubMed
Yazulla, S. (1986). GABAergic mechanisms in the retina. Progress in Retinal Research 5, 1–52.CrossRefGoogle Scholar
Zhang, D., Pan, Z.H., Zhang, X., Brideau, A.D. and 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.CrossRefGoogle ScholarPubMed
Zhang, J. & Slaughter, M.M. (1995). Preferential suppression of the ON pathway by GABAC receptors in the amphibian retina. Journal of Neurophysiology 74, 1583–1592.CrossRefGoogle ScholarPubMed
Zhou, Z.J. & Fain, G.L. (1995). Neurotransmitter receptors of starburst amacrine cells in rabbit retinal slices. Journal of Neuroscience 15, 5334–5345.CrossRefGoogle ScholarPubMed