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

  • Stephen C. Massey (a1), David M. Linn (a2), Christopher A. Kittila (a1) and Wajid Mirza (a1)
  • DOI:
  • Published online: 01 June 2009

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.

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A. Ames & F.B. Nesbett (1981). In vitro retina as an experimental model of the central nervous system. Journal of Neurochemistry 37, 867877.

J. Arnt & P. Krogsgaard-Larsen (1979). GABA agonists and potential antagonists related to muscimol. Brain Research 177, 395400.

J.L. Barker , R.N. McBurney & D.A. Mathers (1983). Convulsant-induced depression of amino acid responses in mouse culture spinal neurones studied under voltage clamp. British Journal of Pharmacology 80, 619630.

H.B. Barlow & W.R. Levick (1965). The mechanism of directionally selective units in rabbit's retina. Journal of Physiology (London) 178, 477504.

J.A. Beutler , E.W. Karbon , A.N. Brubaker , R. Malik , D.R. Curtis & S.J. Enna (1985). Securinine alkaloids: A new class of GABA receptor antagonist. Brain Research 330, 135140.

J. Bormann (1988). Electrophysiology of GABAA and GABAb receptor subtypes. Trends in Neuroscience 11, 112116.

J. Bormann & A. Feigenspan (1995). GABAC receptors. Trends in Neuroscience 18, 515519.

N. Brecha , D. Johnson , L. Peichl & H. Wässle (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, 61876191.

J.P. Chambon , P. Feltz , M. Heaulme , S. Restle , R. Schlichter , K. Biziere & C.G. Wermuth (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, 18321836.

J.R. Cunningham & M.J. Neal (1983). Effect of γ-aminobutyric acid agonists, glycine, taurine and neuropeptides on acetylcholine release from the rabbit retina. Journal of Physiology (London) 362, 5167.

D.R. Curtis , A.W. Duggan , D. Felix & G.A.R. Johnston (1971). Bicuculline, an antagonist of GABA and synaptic inhibition in the spinal cord of the cat. Brain Research 32, 6996.

D.R. Curtis & R. Malik (1985). Glycine antagonism by RU 5135. European Journal of Pharmacology 110, 383384.

M. Desarmenien , E. Desaulles , P. Feltz & M. Hamann (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, 287298.

E.V. Famiglietti (1983 a). On and Off pathways through amacrine cells in mammalian retina: The synaptic connections of ‘starburst’ amacrine cells. Vision Research 23, 12651279.

E.V. Famiglietti (1983 b). ‘Starburst’ amacrine cells and cholinergic neurons: Mirror-symmetric ON and OFF amacrine cells of rabbit retina. Brain Research 261, 138144.

A. Feigenspan & J. Bormann (1994). Differential pharmacology of GABAA and GABAC receptors on rat retinal bipolar cells. European Journal of Pharmacology 288, 97104.

A. Feienspan , H. & J. Bormann (1993). Pharmacology of ABA receptor Cl channels in rat retinal bipolar cells. Nature 361, 159162.

J.M. Fritschy & H. Mohler (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.

B.H. Gahwiler , R. Maurer & H.J. Wuthrich (1984). Pitrazepin, a novel GABAa antagonist. Neuroscience Letters 45, 311316.

U. Greferath , U. Grünert , F. Müller & H. Wässle (1994 b). Localization of GABAA receptors in the rabbit retina. Cell Tissue Research 276, 295307.

M. Heaulme , J.P. Chambon , R. Leyris , J.C. Molimard , C.G. Wermuth & K. Biziere (1986). Biochemical characterization of the interaction of three pyridazinyl-GABA derivatives with the GABA-A receptor site. Brain Research 384, 224231.

M. Heaulme , J.P. Chambon , R. Leyris , C.G. Wermuth & K. Biziere (1987). Characterization of the binding of [3H]SR 95531, a GABAA antagonist, to rat brain membranes. Journal of Neurochemistry 48, 16771686.

P. Krogsgaard-Larsen , H. Hjeds , D.R. Curtis , J.D. Leah & M.J. Peet (1982). Glycine antagonists structurally related to muscimol, THIP, or isoguvacine. Journal of Neurochemistry 39, 13191324.

R.L. Macdonald & R.W. Olsen (1994). GABAA receptor channels. Annual Review of Neuroscience 17, 569602.

R.L. Marc , W.K. Stell , D. Bok & D.M. Lam (1978). GABA-ergic pathways in the goldfish retina. Journal of Comparative Neurology 182, 221245.

R.H. Masland & J.W. Mills (1979). Autoradiographic identification of acetylcholine in the rabbit retina. Journal of Cell Biology 83, 159178.

R.H. Masland , J.W. Mills & S.A. Hayden (1984). Acetylcholine-synthesizing amacrine cells: Identification and selective staining by using autoradiography and fluorescent markers. Proceedings of the Royal Society B (London) 223, 79100.

S.C. Massey & M.J. Neal (1979). The light-evoked release of acetylcholine from the rabbit retina in vivo and its inhibition by GABA. Journal of Neurochemistry 32, 13271329.

S.C. Massey & D.A. Redburn (1987). Transmitter circuits in the vertebrate retina. Progress in Neurobiology 28, 5596.

R.T. McCabe , J.K. Wamsley , J.P. Yezuita & R.W. Olsen (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, 163173.

J.C. Michaud , J.M. Mienville , J.P. Chambon & K. Biziere (1986). Interactions between three pyridazinyl-GABA derivatives and central GABA and glycine receptors in the rat, an in vivo microiontophoretic study. Neuropharmacology 25, 11971203.

R.F. Miller , R.A. Zalutsky & S.C. Massey (1986). A perfused rabbit retina preparation suitable for pharmacological studies. Journal of Neuroscience Methods 16, 309322.

R.W. Olsen (1984). γ-Aminobutyric acid receptor binding antagonism by the amidine steroid RU 5135. European Journal of Pharmacology 103, 333.

H. Qian & J.E. Dowling (1993). Novel GABA responses from rod-driven retinal horizontal cells. Nature 361, 162164.

M.A. Simmonds (1980). Evidence that bicuculline and picrotoxin act at separate sites to antagonize γ-aminobutyric acid in rat cuneate nucleus. Neuropharmacology 19, 3945.

C.G. Wermuth & K. Biziere (1986). Pyridazinyl-GABA derivatives: A new class of synthetic GABAA antagonists. Trends in Pharmacological Sciences 7, 421424.

I. Worms (1979). Neuropharmacological spectrum of muscimol. Life Science 25, 607636.

H.J. Wyatt & N.W. Daw (1976). Specific effect of neurotransmitter antagonists on ganglion cells in rabbit retina. Science 191, 204205.

S. Yazulla (1986). GABAergic mechanisms in the retina. Progress in Retinal Research 5, 152.

D. Zhang , Z.H. Pan , X. Zhang , A.D. Brideau and S.A. Lipton (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, 1175611760.

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