Abstract
In the central nervous system (CNS), the inhibitory transmitter GABA interacts with three subtypes of GABA receptors, type A, type B, and type C. Historically, GABA receptors have been classified as either the inotropic GABAA receptors or the metabotropic GABAB receptors. Over the past 10 yr, studies have shown that a third class, called the GABAC receptor, also exists. GABAC receptors are found primarily in the vertebrate retina and to some extent in other parts of the CNS. Although GABAA and GABAC receptors both gate chloride channels, they are pharmacologically, molecularly, and functionally distinct. The ρ subunit of the GABAC receptor, which has about 35% amino acid homology to GABAA receptor subunits, was cloned from the retina and, when expressed inXenopus oocytes, has properties similar to retinal GABAC receptors. There are probably distinct roles for GABAC receptors in the retina, because they are found on only a subset of neurons, whereas GABAA receptors are ubiquitous. This article reviews recent electrophysiological and molecular studies that have characterized the unique properties of GABAC receptors and describes the roles that these receptors may play in visual information processing in the retina.
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Hill D. R. and Bowery N. G. (1981)3H-Baclofen and3H-GABA bind to bicuculline-insensitive GABAB sites in rat brain.Nature 290, 149–152.
Ortells M. O. and Lunt G. G. (1995) Evolutionary history of the ligand-gated ion-channel superfamily of receptors.Trends Neurosci. 18, 121–127.
Olsen R. W. and Tobin A. J. (1990) Molecular biology of GABAA receptors.FASEB J. 4, 1469–1480.
Wisden W. and Seeburg P. H. (1992) GABAA receptor channels: from subunits to functional entities.Curr. Opin. Neurobiol. 2, 263–269.
Drew C. A., Johnston G. A. R., and Weatherby R. P. (1984) Bicuculline-insensitive GABA receptors: studies on the binding of (−)-baclofen to rat cerebellar membranes.Neurosci. Lett. 52, 317–321.
Johnston G. A. R. (1986) Multiplicity of GABA receptors.Rec. Biochem. Methodol. 5, 57–71.
Johnston G. A. R., Curtis D. R., Beart P. M., Game C. J. A., McCulloch R. M., and Twitchin B. (1975)Cis- andTrans-4-aminocrotonic acid as GABA analogues of restricted conformation.J. Neurochem. 24, 157–160.
Sivilotti L. and Nistri A. (1989) Pharmacology of a novel effect of γ-aminobutyric acid on the frog optic tectum in vitro.Eur. J. Pharmacol. 164, 205–212.
Feigenspan A., Wassle H., and Bormann J. (1993) Pharmacology of GABA receptor Cl-channels in rat retinal bipolar cells.Nature 361, 159–162.
Qian H. and Dowling J. E. (1993) Novel GABA responses from rod-driven retinal horizontal cells.Nature 361, 162–164.
Nistri A. and Sivilotti L. (1985) An unusual effect of γ-aminobutyric acid on synaptic transmission of frog tectal neurones in vitro.Br. J. Pharmacol. 85, 917–921.
Arakawa T. and Okada Y. (1988) Excitatory and inhibitory action of GABA on synaptic transmission in slices of guinea pig superior colliculus.Eur. J. Pharmacol. 158, 217–224.
Strata F. and Cherubini E. (1994) Transient expression of a novel type of GABA response in rat CA3 hippocampal neurones during development.J. Physiol. (Lond.) 480, 493–503.
Heidelberger R. and Matthews G. (1991) Inhibition of calcium influx and calcium current by γ-aminobutyric acid in single synaptic terminals.Proc. Natl. Acad. Sci. USA 88, 7135–7139.
Johnston G. A. R., Allan R. D., Benton A. D., Chen Chow S., Drew C. A., Hiern B. P., Holan G., Kazlauskas R., Rzezniczak H., and Weatherby R. P. (1984) GABA receptors and related binding sites.IUPHAR 9th Int. Congr. Pharmacol. Proc. 3, 179–183.
Cutting G. R., Lu L., O’Hara B. F., and Kasch L. M. (1991) Cloning of the γ-aminobutyric acid (GABA) ρ1 cDNA: a GABA receptor subunit highly expressed in the retina.Proc. Natl. Acad. Sci. USA 88, 2673–2677.
Polenzani L., Woodward R. M., and Miledi R. (1991) Expression of mammalian γ-aminobutyric acid receptors with distinct pharmacology inXenopus oocytes.Proc. Natl. Acad. Sci. USA 88, 4318–4322.
Shimada S., Cutting G., and Uhl G. R. (1992) γ-Aminobutyric acid a or c receptor? γ-Aminobutyric acid ρ1 receptor RNA induces bicuculline-, barbiturate-, and benzodiazepine-insensitive γ-aminobutyric acid responses inXenopus oocytes.Mol. Pharmacol. 41, 683–687.
Woodward R. M., Polenzani L., and Miledi R. (1992) Characterization of bicuculline/balofen-insensitive γ-aminobutyric acid receptors expressed inXenopus oocytes. I. Effects of Cl− channel inhibitors.Mol. Pharmacol. 42, 165–173.
Sigel E., Baur R., Trube G., Mohler H., and Malherbe P. (1990) The effect of subunit composition of rat brain GABAA receptors on channel function.Neuron 5, 703–711.
Verdoorn T. A., Draguhn A., Ymer S., Seeburg P. H., and Sakmann B. (1990) Functional properties of recombinant rat GABAA receptors depend upon subunit composition.Neuron 4, 919–928.
Kusama T., Spivak C. E., Whiting P., Dawson V. L., Schaeffer J. C., and Uhl G. R. (1993) Pharmacology of GABA ρ1 and GABA α/β receptors expressed inXenopus oocytes and Cos cells.Br. J. Pharmacol. 109, 200–206.
Zhang D., Pan Z.-H., Zhang X., Brideau A. D., and Lipton S. A. (1995) Cloning of a γ-aminobutyric acid type C receptor subunit in rat retina with a methionine residue critical for picrotoxin channel block.Proc. Natl. Acad. Sci. USA 92, 11,756–11,760.
Liu Y. and Lasater E. M. (1994) Multiple GABA receptors of ganglion cells in the turtle retina.Invest. Ophthalmol. Visual Sci. Suppl. 35, 2154.
Zhang J. and Slaughter M. M. (1995) Preferential suppression of ON pathway by GABAC receptors in the amphibian retina.J. Neurophysiol. 74, 1583–1592.
Dong C.-J., Picaud S. A., and Werblin F. S. (1994) GABA transporters and GABAC-like receptors on catfish cone—but not rod-driven horizontal cells.J. Neurosci. 14, 2648–2658.
Lukasiewicz P. D., Maple B. R., and Werblin F. S. (1994) A novel GABA receptor on bipolar cell terminals in the tiger salamander retina.J. Neurosci. 14, 1201–1212.
Slaughter M. M. and Bai S.-H. (1989) Differential effects of baclofen on sustained and transient cells in the mudpuppy retina.J. Neurophysiol. 61, 374–381.
Maguire G., Lukasiewicz P., and Werblin F. (1989) Amacrine cell interactions underlying the response to change in the tiger salamander retina.J. Neurosci. 9, 726–735.
Matthews G., Ayoub G. S., and Heidelburger R. (1994) Presynaptic inhibition by GABA is mediated via two distinct GABA receptors with novel pharmacology.J. Neurosci. 14, 1079–1090.
Pan Z.-H. and Lipton S. A. (1995) Multiple GABA receptor subtypes mediate inhibition of calcium influx at rat retinal bipolar cell terminals.J. Neurosci. 15, 2668–2679.
Benson J. A. (1988) Bicuculline blocks the response to acetylcholine and nicotine but not muscarine or GABA in isolated insect neuronal somata.Brain Res. 458, 65–71.
Benson J. A. (1989) A novel GABA receptor in the heart of a primitive arthropod,Limulus polyphemus.J. Exp. Biol. 147, 421–438.
Darlison M. G. (1992) Invertebrate GABA and glutamate receptors: molecular biology reveals predictable structures but some unusual pharmacologies.TINS 15, 469–474.
ffrench-Constant R. H., Rocheleau T. A., Steichen J. C., and Chalmers A. E. (1993) A point mutation inDrosophila GABA receptors confers insecticide resistance.Nature 363, 449–451.
Harvey R. J., Vreugdenhil E., Zaman S. H., Bhandal N. S., Usherwood P. N., Barnard E. A., and Darlison M. G. (1991) Sequence of a functional invertebrate GABAA receptor subunit which can form a chimeric receptor with a vertebrate alpha subunit.EMBO J. 10, 3239–3245.
Zaman S. H., Harvey R. J., Barnard E. A., and Darlison M. G. (1992) Unusual effects of benzodiazepines and cyclodiene insecticides on an expressed invertebrate GABAA receptor.FEBS Lett. 307, 351–354.
Woodward R. M., Polenzani L., and Miledi R. (1993) Characterization of bicuculline/balofeninsensitive (ρ-like)γ-aminobutyric acid receptors expressed inXenopus oocytes. II. Pharmacology of γ-aminobutyric acidA and γ-aminobutyric acidB receptor agonists and antagonists.Mol. Pharmacol. 43, 609–625.
Qian H. and Dowling J. E. (1994) Pharmacology of novel GABA receptors found on rod horizontal cells of the white perch retina.J. Neurosci. 14, 4299–4307.
Wang Tian-L., Guggino W. B., and Cutting G. R. (1994) A novel γ-aminobutyric acid receptor subunit (p2) cloned from human retina forms bicuculline-insensitive homo-ologomeric receptors inXenopus oocytes.J. Neurosci. 14, 6524–6531.
Cutting G. R., Curristin S., Zoghbi H., O’Hara B., Seldin M. F., and Uhl G. R. (1992) Identification of a putative γ-aminobutyric acid (GABA) receptor subunit rho2 cDNA and localization of the genes encoding rho2 (GABRR2) and rho1 (GABRR1) to human chromosome 6q14-q21 and mouse chromosome 4.Genomics 12, 801–806.
Wang Tian-L., Hackam A. S., Guggino W. B., and Cutting G. R. (1995) A single amino acid in γ-aminobutyric acid p1 receptors affects competitive and noncompetitive components of picrotoxin inhibition.Proc. Natl. Acad. Sci. USA 92, 11,751–11,755.
Enz R. and Bormann J. (1995) A single point mutation decreases picrotoxinin sensitivity of the human GABA receptor p1 subunit.NeuroReport 6, 1569–1572.
Dong C.-J. and Werblin F. S. (1995) Zinc downmodulates the GABAC receptor current in cone horizontal cells acutely isolated from the catfish retina.J. Neurophysiol. 73, 916–919.
Calvo D. J., Vaquez A. E., and Miledi R. (1994) Cationic modulation of ρ1-type γ-aminobutyrate receptors expressed inXenopus oocytes.Proc. Natl. Acad. Sci. USA 91, 12,725–12,729.
Chang Y., Amin J., and Weiss D. S. (1995) Zinc is a mixed antagonist of homomeric ρ1 γ-aminobutyric acid-activated channels.Mol. Pharmacol. 47, 595–402.
Draguhn A., Verdorn T. A., Ewert M., Seeburg P. H., and Sakmann B. (1990) Functional and molecular distinction between recombinant rat GABAA receptor subtypes by Zn++.Neuron 5, 781–788.
Amin J. and Weiss D. S. (1994) Homomeric ρ1 GABA channels: activation properties and domains.Rec. Chann. 2, 227–236.
Enz R., Brandstatter J. H., Hartviet E., Wassle H., and Bormann J. (1995) Expression of GABA receptors p1 and p2 subunits in the retina and brain of the rat.Eur. J. Neurosci. 7, 1495–1501.
Albrecht B. E. and Darlison M. G. (1995) Localization of the p1- and p2-subunit messenger RNAs in chick retina by in situ hybridization predicts the existence of gamma amino butyric acid type C receptor subtypes.Neurosci. Lett. 189, 155–158.
Dowling J. E. (1987)The Retina: An Approachable Part of the Brain. The Belknap Press of Harvard University Press, Cambridge, MA.
Tachibana M. and Kaneko A. (1984) γ-Aminobutyric acid acts at axon terminals of turtle photoreceptors: difference in sensitivity among cell types.Proc. Natl. Acad. Sci. USA 81, 7961–7964.
Kaneko A. and Tachibana M. (1986) Effects of gamma-aminobutyric acid on isolated cone photoreceptors of the turtle retina.J. Physiol. (Lond.) 373, 443–461.
Wu S. M. (1991) Input-output relations of the feedback synapse between horizontal cells and cones in the tiger salamander retina.J. Neurophysiol. 65, 1197–1206.
Qian H. and Dowling J. E. (1995) GABAA and GABAC receptors on hybrid bass retinal bipolar cells.J. Neurophysiol. 74, 1920–1928.
Feigenspan A. and Bormann J. (1994) Differential pharmacology of GABAA and GABAC receptors on rat retinal bipolar cells.Eur. J. Pharmacol. 288, 97–104.
Belgium J. H., Dvorak D. R., and McReynolds J. S. (1984) Strychnine blocks transient but not sustained inhibition in mudpuppy retinal ganglion cells.J. Physiol. (Lond.) 354, 273–286.
Karschin A. and Wassle H. (1990) Voltage- and transmitter-gated currents in isolated rod bipolar cells of rat retina.J. Neurophys. 63, 860–876.
Wellis D. P. and Werblin F. S. (1995) Dopamine modulates GABAC receptors mediating inhibition of calcium entry into and transmitter release from bipolar cell terminals in tiger salamanders.J. Neurosci. 15, 4748–4761.
Tachibana M., Okada T., Kobayashi K., and Picolino M. (1993) Dihydropyridine-sensitive calcium current mediate neurotransmitter release from bipolar cells of the goldfish retina.J. Neurosci. 13, 2898–2909.
Marc R. E., Stell W. K., Bok D., and Lam D. M. K. (1978) GABA-ergic pathways in the goldfish retina.J. Comp. Neurol. 182, 221–246.
Yazulla S., Studholme K. M., and Wu, J.-Y. (1987) GABAergic input to the synaptic terminals of mb1 bipolar cells in the goldfish retina.Brain Res. 411, 400–405.
Chun M. and Wassle H. (1989) GABA-like immunoreactivity in the cat retina: electron microscopy.J. Comp. Neural. 279, 55–67.
Pourcho R. and Owczarzak M. (1989) Distribution of GABA immunoreactivity in the cat retina: a light- and electron-microscopic study.Vis. Neurosci. 2, 425–435.
Lukasiewicz P. D. and Werblin F. S. (1994) A novel GABA receptor modulates synaptic transmission from bipolar to ganglion and amacrine cells in the tiger salamander retina.J. Neurosci. 14, 1213–1223.
Murakami M., Shimoda Y., Kakatani K., Miyachi E.-I., and Wantanbe S.-I. (1982) GABA mediated negative feedback from horizontal cells to cones in the carp retina.Jpn. J. Physiol. 32, 911–926.
Toyoda J.-I. and Fujimoto M. (1983) Analyses of neural mechanisms mediating the effect of horizontal cell polarization.Vision Res. 23, 1143–1150.
Takahashi K., Miyoshi S., and Kaneko A. (1994) Two components of GABA-induced currents in catfish retinal horizontal cells.Jpn. J. Physiol. 44(Suppl. 2), s141–144.
Kammermans M. and Werblin F. (1992) GABA-mediated positive autofeedback loop controls horizontal cell kinetics in tiger salamander retina.J. Neurosci. 12, 2451–2463.
Wu S. M., Qiao X., Noebels J. L., and Yang X. L. (1993) Localization and modulatory actions of zinc in vertebrate retina.Vision Res. 33, 2611–2616.
Tachibana M. and Kaneko A. (1987) γ-Aminobutyric acid exerts a local inhibitory action on the axon terminal of bipolar cells: evidence for negative feedback from amacrine cells.Proc. Natl. Acad. Sci. USA 84, 3501–3505.
Dong C.-J. and Werblin F. S. (1994) Dopamine modulation of GABAC receptor function in an isolated retinal neuron.J. Neurophysiol. 71, 1258–1260.
Feigenspan A. and Bormann J. (1994) Modulation of GABAC receptors in rat retinal bipolar cells by protein kinase C.J. Physiol. (Lond.) 481, 325–330.
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Lukasiewicz, P.D. GABAC receptors in the vertebrate retina. Mol Neurobiol 12, 181–194 (1996). https://doi.org/10.1007/BF02755587
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DOI: https://doi.org/10.1007/BF02755587