Skip to main content
SpringerLink
Log in

GABA uptake by purified avian Müller glia cells in culture

  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

Abstract

GABA is the main inhibitory aminoacid transmitter present in neurons and glial cells. Its uptake is carried out by specific high-affinity Na+/Cl− dependent transporters (GATs). It has been reported in the past that, in the avian retina, [3H]GABA appears to be exclusively accumulated by horizontal and amacrine cells in the inner nuclear layer, and also by ganglion cells. Purified chick Müller glia cultures were able to take up [3H]GABA in a Na+ and Cl− dependent way. Increasing GABA concentration increases GABA uptake by these cells, reaching half-maximal transport efficiency (EC50) around 0.3 mM. [3H]GABA uptake by Müller glia neuronal-free cultures was not mediated by neuronal transporters since it was not blocked by NNC-711, but was inhibited by beta-alanine, a specific glial transporter inhibitor. Chick Müller glia in culture express both GAT-1 and GAT-3 GABA transporters. Although mixed neuron-glial dense cultures released GABA upon glutamate, high K+ or veratridine stimulation, Müller glial cells did not release [3H]GABA upon treatment with these agents, suggesting that different from neurons, transporter mediated GABA release is not a common mechanism operating in these cells. The data also suggest that Müller cells take up GABA unidirectionally, which may constitute an important mechanism of inactivating GABA activity mediated by neurons.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Amara S and J Arriza (1993) Neurotransmitter transporters: three distinct gene families.Curr. Opin. Neurobiol. 3, 337–344.

    Article  PubMed  CAS  Google Scholar 

  • Amara S and MJ Kuhar (1993) Neurotransmitter transporters: recent progress.Annu. Rev. Neurosci. 16, 73–93.

    Article  PubMed  CAS  Google Scholar 

  • Beckman ML, EM Bernstein and MW Quick (1998) Protein kinase C regulates the interaction between a GABA transporter and syntaxin 1A.J. Neurosci. 18, 6103–6112.

    PubMed  CAS  Google Scholar 

  • Bernstein EM and MW Quick (1999) Regulation of gammaaminobutyric acid (GABA) transporters by extracellular GABA.J. Biol. Chem. 274, 889–895.

    Article  PubMed  CAS  Google Scholar 

  • Biedermann B, W Eberhardt and W Reichelt (1994) GABA uptake into isolated retinal Müller glial cells of the guineapig defected electrophysiologically.Neuroreport 5, 438–440.

    Article  PubMed  CAS  Google Scholar 

  • Biedermann B, A Bringmann and A Reichenbach (2002) Highaffinity GABA uptake in refinal glial (Müller) cells of the guinea pig: electrophysiological characterization, immunohistochemical localization, and modeling of efficiency.Glia 39, 217–228.

    Article  PubMed  Google Scholar 

  • Birnbaum AD, SK Rohde, H Qian, MR Al-Ubaidi, JH Caldwell and RP Malchow (2005) Cloning, immunolocalization, and functional expression of a GABA transporter from the retina of the skate.Vis. Neurosci. 22, 211–223.

    Article  PubMed  Google Scholar 

  • Borden LA (1996) GABA transporter heterogeneity: pharmacology and cellular localization.Neurochem. Int. 29, 335–356.

    Article  PubMed  CAS  Google Scholar 

  • Brecha NC and C Weigmann (1994) Expression of GAT-1, a high-affinity gamma-aminobutyric acid plasma membrane transporter in the rat retina.J. Comp. Neurol. 345, 602–611.

    Article  PubMed  CAS  Google Scholar 

  • Eringmann A, T Pannicke, J Grosche, M Francke, P Wiedemann, SN Skatchkov, NN Osborne and A Reichenbach (2006) Müller cells in the healthy and diseased retina.Prog. Retin. Eye Res. 25, 397–424.

    Article  Google Scholar 

  • Calaza KC, FG de Mello and PF Gardino (2001) GABA release induced by aspartate-mediated activation of NMDA receptors is modulated by dopamine in a selective subpopulation of amacrine cells.J. Neurocytol. 301, 81–93.

    Google Scholar 

  • Calaza KC, PF Gardino and FG de Mello (2006) Transporter mediated GABA release in the retina: role of excitatory amino acids and dopamine.Neurochem. Int. 49, 769–777.

    Article  PubMed  CAS  Google Scholar 

  • Casini G, DW Rickman and NC Brecha (2006) Expression of the gamma-aminobutyric acid (GABA) plasma membrane transporter-1 in monkey and human retina.Invest. Ophthalmol. Vis. Sci. 47, 1682–1690.

    Article  PubMed  Google Scholar 

  • Cohen-Kfir E, W Lee, S Eskandari and N Nelson (2005) Zinc inhibition of gamma-aminobutyric acid transporter 4 (GAT4) reveals a link between excitatory and inhibitory neurotransmission.Proc. Natl. Acad. Sci. USA 102, 6154–6159.

    Article  PubMed  CAS  Google Scholar 

  • do Nascimento JLM and FG de Mello (1985) Induced release of gamma-aminobutyric acid by a carrier-mediated, highaffinity uptake of L-glutamate in cultured chick retina cells.J. Neurochem. 45, 1820–1827.

    Article  PubMed  Google Scholar 

  • Fischer AJ (2005) Neural regeneration in the chick retina.Prog. Retin. Eye Res. 24, 161–182.

    Article  PubMed  Google Scholar 

  • Fischer AJ and TA Reh (2001) Müller glia are a potential source of neural regeneration in the postnatal chicken retina.Nat. Neurosci. 4, 247–252.

    Article  PubMed  CAS  Google Scholar 

  • Guastella, J, N Nelson, H Nelson, L Czyzyk, S Keynan, MC Davidson, HA Lester and BI Kanner (1990) Cloning and expression of a rat brain GABA transporter.Science 249, 1303–1306.

    Article  PubMed  CAS  Google Scholar 

  • Hamburger V and HL Hamilton (1951) A series of normal stages in the development of chick embryo.J. Morphol. 88, 49–92.

    Article  Google Scholar 

  • Iversen LL and JS Kelly (1995) Uptake and metabolism of gamma-aminobutyric acid by neurones and glial cells.Biochem. Pharmacol. 24, 933–938.

    Article  Google Scholar 

  • Kanner BI (1994) Sodium-coupled neurotransmitter transport: structure, function and regulation.J. Exp. Biol. 196, 237–249.

    PubMed  CAS  Google Scholar 

  • Kim D, MJ Kim, JH Lee, JO Im, YJ Won, S-Y Yoon and HN Hong (2003) Concomitant distribution shift of glial GABA transporter and S100 calcium-binding proteins in the rat retina after kainate-induced excitotoxic injury.Neurosci. Lett. 353, 17–20.

    Article  PubMed  CAS  Google Scholar 

  • Kubrusly RCC, MCC Cunha, RAM Reis, H Soares, ALM Ventura, H Kurtenbach, MCF de Mello and FG de Mello (2005) Expression of functional receptors and transmitter enzymes in cultured Müller cells.Brain Res. 1038, 141–149.

    Article  PubMed  CAS  Google Scholar 

  • Law RM, A Stafford and MW Quick (2000) Functional regulation of gamma-aminobutyric acid transporters by direct tyrosine phosphorylation.J. Biol. Chem. 275, 23986–23991.

    Article  PubMed  CAS  Google Scholar 

  • Liu, Q-R, B López-Corcuera, S Mandiyan, H Nelson and N Nelson (1993) Molecular characterization of four pharm acologically distinct γ-amino butyric acid transporters in mouse brain.J. Biol. Chem. 268, 2106–2112.

    PubMed  CAS  Google Scholar 

  • Marshall J and M Voaden (1974) An autoradiographic study of the cells accumulating3H gamma-aminobutyric acid in the isolated retinas of pigeons and chickens.Invest. Ophthalmol 13, 602–607.

    PubMed  CAS  Google Scholar 

  • Newman EA (2004) Glial modulation of synaptic transmission in the retina.Glia 47, 268–274.

    Article  PubMed  Google Scholar 

  • Newman E and A Reichenbach (1996) The Müller cell: a functional element of the retina.Trends Neurosci 19, 307–312.

    Article  PubMed  CAS  Google Scholar 

  • Perea G and A Araque (2006) Synaptic information processing by astrocytes.J. Physiol. (Paris) 99, 92–97.

    Article  CAS  Google Scholar 

  • Pow DV, RKP Sullivan, SM Williams, HL Scott, PR Dodd and D Finkelstein (2005) Differential expression of the GABA transporters GAT-1 and GAT-3 in brains of rats, cats, monkeys and humans.Cell Tissue Res. 320, 379–392.

    Article  PubMed  CAS  Google Scholar 

  • Quick MW (2002) Substrates regulate gamma-aminobutyric acid transporters in a syntaxin 1A-dependent manner.Proc. Natl. Acad. Sci. USA 99, 5686–5691.

    Article  PubMed  CAS  Google Scholar 

  • Redburn DA and P Madtes Jr (1986) Postnatal development of3H-GABA-accumulating cells in rabbit refina.J. Comp. Neurol. 243, 41–57.

    Article  PubMed  CAS  Google Scholar 

  • Reis RAM, MC Cabral da Silva, NE Loureiro dos Santos, E Bampton, JSH Taylor, FG de Mello and R Linden (2002) Sympathetic neuronal survival induced by retinal trophic factors.J. Neurobiol. 50, 13–23.

    Article  PubMed  CAS  Google Scholar 

  • Sarthy PV (1983) Release of [3H]gamma-aminobutyric acid from glial (Müller) cells of the rat retina: effects of K+, veratridine, and ethylenediamine.J. Neurosci. 3, 2494–2503.

    PubMed  CAS  Google Scholar 

  • Sarthy V and H Ripps (2001)The Retinal Müller Cell — Structure and Function (Kluwer Academic: New York, NY) 278 pp.

    Google Scholar 

  • Schon F and JS Kelly (1975) Selective uptake of [3H]betaalanine by glia: association with glial uptake system for GABA.Brain Res. 86, 243–257.

    Article  PubMed  CAS  Google Scholar 

  • Schousboe A (2000) Pharmacological and functional characterization of astrocytic GABA transport: a short review.Neurochem. Res. 25, 1241–1244.

    Article  PubMed  CAS  Google Scholar 

  • Schousboe A (2003) Role of astrocytes in the maintenance and modulation of glutamatergic and GABAergic neurotransmission.Neurochem. Res. 28, 347–352.

    Article  PubMed  CAS  Google Scholar 

  • Schousboe A, OM Larsson, A Sarup, and HS White (2004) Role of the betaine/GABA transporter (GAT-1/GAT2) for the control of epilepsy.Eur. J. Pharmacol. 500, 281–287.

    Article  PubMed  CAS  Google Scholar 

  • Todd KJ, A Serrano, JC Lacaille and R Robitaille (2006) Glial cells in synaptic plasticity.J. Physiol. (Paris) 99, 75–83.

    Article  CAS  Google Scholar 

  • Won MH, TC Kang and SS Cho (2000) Glial cells in the bird retina: immunochemical detection.Microsc. Res. Tech. 50, 151–160.

    Article  PubMed  CAS  Google Scholar 

  • Wu Q, M Wada, A Shimada, A Yamamoto and T Fujita (2006) Functional characterization of Zn2(+)-sensitive GABA transporter expressed in primary cultures of astrocytes from rat cerebral cortex.Brain Res. 1075, 100–109.

    Article  PubMed  CAS  Google Scholar 

  • Zhao JW, JL Du, JS Li and XL Yang (2000) Expression of GABA transporters on bullfrog retinal Müller cells.Glia 31, 104–117.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratório de Neuroquímica, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

    Clarissa De Sampaio Schitine, Regina Célia Cussa Kubrusly, Ricardo Augusto De Melo Reis, Edna Nanami Yamasaki, Maria Christina Fialho De Mello & Fernando Garcia De Mello

  2. Laboratório de Neurobiologia da Retina, Instituto de Biofisica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brasil

    Edna Nanami Yamasaki

  3. Laboratório de Neurofarmacologia, Departamento de Fisiologiae Farmacologia, Instituto Biomédico, Universidade Federal Fluminense, Rio de Janeiro, Brasil

    Regina Célia Cussa Kubrusly

Authors
  1. Clarissa De Sampaio Schitine
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Regina Célia Cussa Kubrusly
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ricardo Augusto De Melo Reis
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Edna Nanami Yamasaki
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Maria Christina Fialho De Mello
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fernando Garcia De Mello
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Fernando Garcia De Mello.

Rights and permissions

Reprints and permissions

About this article

Cite this article

De Sampaio Schitine, C., Cussa Kubrusly, R.C., De Melo Reis, R.A. et al. GABA uptake by purified avian Müller glia cells in culture. neurotox res 12, 145–153 (2007). https://doi.org/10.1007/BF03033923

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF03033923

Keywords

Search

Navigation