Pharmacology and Physiology of Cl Conductances Activated by GABA in Cultured Mammalian Central Neurons

  • Jeffrey L. Barker
  • N. L. Harrison
  • David G. Owen


Cl permeability mechanisms regulated by neurotransmitters acting via receptor proteins are expressed in a wide variety of excitable tissues throughout all evolutionary forms studied. In vivo the permeability can be regulated physiologically by neurotransmitters like γ-aminobutyric acid (GABA) or glycine acting on receptors at subsynaptic membranes. Synaptically activated Cl flux can be found in the adult at all levels of spinal and supraspinal regions of the mammalian CNS where it usually functions to depress cellular excitability in a transient manner. A brief pause in ambient electrical activity lasting milliseconds is typically recorded during this physiologically elaborated synaptic signal. This in turn usually suppresses secretory activity derived indirectly from Na+ action potential invasion of presynaptic terminals. Thus, synaptic signals involving Cl conductances effectively uncouple central neurons from one another and in so doing shape patterns of cellular excitation and neuronal circuit activity.


Gaba Receptor Glycine Receptor Central Neuron Spinal Neuron Voltage Response 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Ashwood, T. J., Collingridge, G. L., Herron, C. E., and Wheal, H. V., 1987, Voltage-clamp analysis of somatic gamma-aminobutyric acid responses in adult rat hippocampal CAI neurons in vitro, J. Physiol. (London) 384: 27–37.Google Scholar
  2. Barker, J. L., 1983, Chemical excitability in vertebrate central neurons, in: The Clinical Neurosciences, Volume 5 ( W. D. Wills, ed.), Churchill—Livingston, Edinburgh, pp. 121–141.Google Scholar
  3. Barker, J. L., and Harrison, N. L., 1988, Outward rectification of inhibitory postsynaptic currents in cultured rat hippocampal neurons, J. Physiol. (London) 403: 41–55.Google Scholar
  4. Barker, J. L., and McBurney, R. N., 1979a, GABA and glycine may share the same conductance channel on cultured mammalian neurones, Nature 277: 234–236.PubMedCrossRefGoogle Scholar
  5. Barker, J. L., and McBumey, R. N., 1979b, Phenobarbitone modulation of postsynaptic GABA receptor function on cultured mammalian neurons, Proc. R. Soc. London Ser. B 206: 318–326.CrossRefGoogle Scholar
  6. Barker, J. L., and Mathers, D. A., 1981, GABA analogues activate channels of different duration in cultured mouse spinal neurons, Science 212: 358–361.PubMedCrossRefGoogle Scholar
  7. Barker, J. L., and Ransom, B. R., I978a, Amino acid pharmacology of mammalian central neurones grown in tissue culture, J. Physiol. (London) 280: 331–354.Google Scholar
  8. Barker, J. L., and Ransom, B. R., 1978b, Pentobarbitone pharmacology of mammalian central neurones grown in tissue culture, J. Physiol. (London) 280: 355–372.Google Scholar
  9. Barker, J. L., McBumey, R. N., and MacDonald, J. F., 1982, Fluctuation analysis of neutral amino acid responses in cultured mouse spinal neurons, J. Physiol. (London) 322: 365–387.Google Scholar
  10. Barker, J. L., McBumey, R. N., and Mathers, D. A., 1983, Convulsant-induced depression of amino acid responses in cultured mouse spinal neurons studied under voltage clamp, Br. J. Pharmacol. 80: 619–629.PubMedCrossRefGoogle Scholar
  11. Barker, J. L., Harrison, N. L., Lange, G. D., and Owen, D. G., 1987a, Potentiation of gamma-aminobutyric acid-activated chloride conductance by a steroid anesthetic in cultured rat spinal neurones, J. Physiol. (London) 386: 485–501.Google Scholar
  12. Barker, J. L., Dufy, B., Harrington, J. W., Harrison, N. L., MacDermott, A. B., MacDonald, J. F., Owen, D. G., and Vicini, S., 1987b, Signals transduced by gamma-aminobutyric acid in cultured central nervous system neurons and thyrotropin releasing hormone in clonal pituitary cells, Ann. N.Y. Acad. Sci. 494: 1–38.PubMedCrossRefGoogle Scholar
  13. Bormann, J., Hamill, O. P., and Sakmann, B., 1987, Mechanism of anion permeation through channels gated by glycine and gama-aminobutyric acid in mouse cultured spinal neurones, J. Physiol. (London) 385: 243–286.Google Scholar
  14. Bührle, C. P., and Sonnhof, U., 1985, The ionic mechanism of postsynaptic inhibition in motoneurones of the frog spinal cord, Neuroscience 14: 581–592.PubMedCrossRefGoogle Scholar
  15. Collingridge, G. L., Gage, P. W., and Robertson, B., 1984, Inhibitory postsynaptic currents in rat hippocampal CAI neurones, J. Physiol. (London) 356: 551–564.Google Scholar
  16. Faber, D. S., and Korn, H., 1987, Voltage-dependence of glycine-actived Cl-channels: A potentiometer for inhibition, J. Neurosci. 7: 807–811.PubMedGoogle Scholar
  17. Fiszman, M., Novotny, E. A., Lange, G. D., and Barker, J. L., 1988, Functional GABAA receptors are expressed in the early embryonic rat hippocampus and striatum, FASEB J. 2: A1734.Google Scholar
  18. Gray, R., and Johnston, D., 1985, Rectification of single GABA-gated chloride channels in adult hippocam-pal neurons, J. Neurophysiol. 54: 134–142.PubMedGoogle Scholar
  19. Grenningloh, G., Rienitz, A., Schmitt, B., Methfessel, C., Zenson, M., Bayreuther, K., Gundelfinger, E. D., and Betz, H., 1987, The strychnine-binding subunit of the glycine receptor shows homology with nicotinic acetylcholine receptors, Nature 328: 215–220.PubMedCrossRefGoogle Scholar
  20. Hamill, O. P., Bormann, J., and Sakmann, B., 1983, Activation of multiple-conductance state chloride channels in spinal neurones by glycine and GABA, Nature 305: 805–808.PubMedCrossRefGoogle Scholar
  21. Harrison, N. L., Vicini, S., and Barker, J. L., I987a, A steroid anesthetic prolongs inhibitory postsynaptic currents in cultured rat hippocampal neurons, J. Neurosci. 7: 604–609.Google Scholar
  22. Harrison, N. L., Majewska, M. D., Harrington, J. W., and Barker, J. L., 1987b, Structure-activity relationships for steroid interaction with the gamma-aminobutyric acidA receptor complex, J. Pharmacol. Exp. Ther. 241: 346–353.PubMedGoogle Scholar
  23. Jackson, M. B., Lecar, H., Mathers, D. A., and Barker, J. L., 1982, Single channel currents activated by GABA, muscimol, and (-) pentobarbital in cultured mouse spinal neurons, J. Neurosci. 2: 889–894.PubMedGoogle Scholar
  24. Levitan, E. S., Blair, A. C. L., Dionne, V. E., and Barnard, E. A., 1988, Biophysical and pharmacological properties of cloned GABAA receptor subunits expressed in Xenopus oocytes, Neuron 1: 773–781.PubMedCrossRefGoogle Scholar
  25. McBurney, R. N., and Barker, J. L., 1978, GABA-induced conductance fluctuations in spinal neurons, Nature 274: 596–597.PubMedCrossRefGoogle Scholar
  26. MacDonald, J. F., Owen, D. G., and Barker, J. L., 1985, Voltage-sensitive spontaneously-occurring chloride channels in cultured spinal neurons, J. Neurosci. Abstr. 11: 200.Google Scholar
  27. MacDonald, R. L., Rogers, C. J., and Twyman, R. E., 1989, Kinetic properties of the GABAA receptor main conductance state of mouse spinal cord neurons in culture, J. Physiol. (London) 410: 479–499.Google Scholar
  28. Majewska, M. D., Harrison, N. L., Schwartz, R. D., Barker, J. L., and Paul, S. M., 1986, Steroid hormone metabolites are barbiturate-like modulators of the GABA receptor, Science 323: 1004–1007.CrossRefGoogle Scholar
  29. Mandler, R. N., Schaffner, A. E., Novotny, E. A., Lange, G. D., and Barker, J. L., 1988, Functional GABA and glycine receptors precede glutamate receptors during the development of the rat spinal cord, Soc. Neurosci. Abstr. 13: 12–26.Google Scholar
  30. Mathers, D. A., 1985a, Spontaneous and GABA-induced single-channel currents in cultured murine spinal neurons, Can. J. Physiol. Pharmacol. 63: 1228–1233.PubMedCrossRefGoogle Scholar
  31. Mathers, D. A., 1985b, Pentobarbital promotes bursts of gamma-aminobutyric acid-activated single channel currents in cultured mouse central neurons, Neurosci. Lett. 60: 121–126.PubMedCrossRefGoogle Scholar
  32. Mathers, D. A., and Barker, J. L., 1981a, GABA- and glycine-activated channels in cultured mouse spinal neurons require the same energy to close, Brain Res. 224: 441–445.PubMedCrossRefGoogle Scholar
  33. Mathers, D. A., and Barker, J. L., 198 lb, GABA and muscimol open channels of different lifetimes on cultured mouse spinal neurons, Brain Res. 204: 242–247.Google Scholar
  34. Olsen, R. W., and Snowman, A., 1983, [3}1] Bicuculline methochloride binding to low-affinity gammaaminobutyric acid receptor sites, J. Neurochem. 41: 1653–1663.Google Scholar
  35. Ozawa, S., and Yuzaki, M., 1984, Patch-clamp studies of Cl-channels activated by gamma-aminobutyric acid in cultured hippocampal neurones of the rat, Neurosci. Res. 1: 275–293.PubMedCrossRefGoogle Scholar
  36. Pritchett, D. B., Sontheimer, H., Gorman, C. M., Kettenmann, H., Seeburg, P. H., and Scholfield, P. R., 1988, Transient expression shows ligand gating and allosteric potentiation of GABAA receptor subunits, Science 242: 1306–1308.PubMedCrossRefGoogle Scholar
  37. Redmann, G. A., and Barker, J. L., 1984, Diazepam and voltage increase GABA-activated CL — ion channel opening kinetics in cultured mouse spinal neurons, Soc. Neurosci. Abstr. 10: 642.Google Scholar
  38. Sakmann, B., Hamill, O. P., and Bormann, J., 1983, Patch-clamp measurements of elementary chloride currents activated by the putative inhibitory transmitters GABA and glycine in mammalian spinal neurons, J. Neural Transm. (Suppl.) 1: 83–95.Google Scholar
  39. Scholfield, P. R., Darlison, M. G., Fujita, N., Burt, D. R., Stephenson, F. A., Rodriguez, H., Rhee, L. M., Ramachandram, J., Reale, J., Glencorse, T. A., Seeburg, P. H., and Barnard, E. A., 1987, Sequence and functional expression of the GABAA receptor shows a ligand-gated receptor super-family, Nature 328: 221–223.CrossRefGoogle Scholar
  40. Segal, M., and Barker, J. L., 1984a, Rat hippocampal neurons in culture: Properties of GABA-activated Cl—ion conductance, J. Neurophysiol. 52: 500–515.Google Scholar
  41. Segal, M., and Barker, J. L., 1984b, Rat hippocampal neurons in culture: Voltage clamp analysis of inhibitory connections, J. Neurophysiol. 52: 469–487.PubMedGoogle Scholar
  42. Study, R. E., and Barker, J. L., 1981, Diazepam and (—) pentobarbital: Fluctuation analysis reveals different mechanisms for potentiation of GABA responses in cultured central neurons, Proc. Natl. Acad. Sci. USA 78: 7180–7184.PubMedCrossRefGoogle Scholar
  43. Taleb, A., Trouslard, J., Demeneix, B. A., Feltz, P., Bossu, J.-L., Dupont, J.-L., and Feltz, A., 1987, Spontaneous and GABA-evoked chloride channels on pituitary intermediate lobe cells and their internal Ca requirements, Pfluegers Arch. 409: 620–631.CrossRefGoogle Scholar
  44. Triller, A., Cluzeaud, R., and Korn, H., 1987, Gamma-aminobutyric acid-containing terminals can be apposed to glycine receptors at central synapses, J. Cell Biol. 104: 947–956.PubMedCrossRefGoogle Scholar
  45. Vicini, S., Alho, H., Costa, E., Mienville, J.-M., Santi, M. R., and Vaccarino, F. M., 1986, Modulation of gamma-aminobutyric acid-mediated inhibitory synaptic currents in dissociated cortical cell cultures, Proc. Natl. Acad. Sci. USA 83: 9269–9273.PubMedCrossRefGoogle Scholar
  46. Vicini, S., Mienville, J.-M., and Costa, E., 1987, Actions of benzodiazepine and beta-carboline derivatives on gamma-aminobutyric acid-activated Cl — channels recorded from membrane patches of neonatal rat cortical neurons in culture, J. Pharmacol. Exp. Ther. 243: 1195–1201.PubMedGoogle Scholar
  47. Weiss, D. S., 1988, Membrane potential modulates the activation of GABA-gated channels, J. Neurophysiol. 59: 514–527.PubMedGoogle Scholar
  48. Weiss, D. S., Barnes, E. M., and Hablitz, J. J., 1988, Whole-cell and single-channel recordings of GABAgated currents in cultured chick cerebral neurons, J. Neurophysiol. 59: 495–513.PubMedGoogle Scholar
  49. Wong, E. H. F., and Iversen, L. L., 1985, Modulation of [’H] diazepam binding in rat cortical membranes by GABAA agonists, J. Neurochem. 44: 1162–1167.PubMedCrossRefGoogle Scholar
  50. Yang, J. S.-J., and Olsen, R. W., 1987, Gamma-aminobutyric acid receptor binding in fresh mouse brain membranes at 22° C ligand-induced changes in affinity, Mol. Pharmacol. 32: 266–277.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1990

Authors and Affiliations

  • Jeffrey L. Barker
    • 1
  • N. L. Harrison
    • 1
  • David G. Owen
    • 1
  1. 1.Laboratory of Neurophysiology, National Institute of Neurological Disorders and Stroke, National Institutes of HealthBethesdaUSA

Personalised recommendations