Skip to main content
NCBI home page
Cellular and Molecular Neurobiology logoLink to Cellular and Molecular Neurobiology
. 1991 Jun;11(3):333–346. doi: 10.1007/BF00713277

Can Cl− ions be extruded from aγ-aminobutyric (GABA)-acceptive nerve cell via GABAA receptors on the plasma membrane cytoplasmic side?

Aroldo Cupello 1,2,✉, Anita Palm 1,2, Maria V Rapallino 1,2, Holger Hydén 1,2
PMCID: PMC11567490  PMID: 1651163

Abstract

  1. In this commentary we discuss results obtained by a micromethod for the study of Cl− permeability across single nerve membranes from rabbit Deiters' neurons.

  2. These results showed the presence of GABAA receptors on the nerve cell membrane cytoplasmic side.

  3. We could show that these receptor complexes have a higher affinity for GABA than their extracellularly facing counterparts. Moreover, they present a phenomenon of desensitization. Another distinct property is that upon activation by GABA, they expose positive charges at their cytoplasmic mouths.

  4. We propose that these receptor complexes could functionin situ as a device for extruding Cl− anions from the nerve cell interior. This phenomenon would create an electrochemical gradient for Cl− penetration into the cell upon the action of extracellular GABA, after its presynaptic release.

Key words: Cl− ions, Cl− electrochemical gradient, cytoplasmic side GABAA receptors, Deiters' neuron

References

  1. Bührle, C. P., and Sonnhof, U. (1985). The ionic mechanism of post-synaptic inhibition in motoneurons of the frog spinal cord.Neuroscience14581–592. [DOI] [PubMed] [Google Scholar]
  2. Cupello, A., Larsson, A., Palm, A., and Rapallino, M. V. (1988). A microelectrophoretic method for the evaluation of GABA transaminase activity.Neurochem. Res.13601–603. [DOI] [PubMed] [Google Scholar]
  3. Dani, J. A. (1986). Ion-channel entrances influence permeation: Net charge, size, shape, and binding considerations.Biophys. J.49607–618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dani, J. A. (1988). Ionic permeability and the open channel structure of the nicotinic acetylcholine receptor. InTransport Through Membranes: Carriers, Channels and Pumps (A. Pullmanet al., eds.), Kluwer Academic, pp. 297-319.
  5. Enna, S. J., and Gallagher, J. P. (1983). Biochemical and electrophysiological characteristics of mammalian GABA receptors.Int. Rev. Neurobiol.24181–206. [DOI] [PubMed] [Google Scholar]
  6. Hydén, H., and Cupello, A. (1987). Inhibition in the mammalian brain: A new theory of GABA mechanism of action.Acta Physiol. Scand.130 (Suppl. 561):1–77. [PubMed] [Google Scholar]
  7. Hydén, H., Larsson, S., and Lange, P. W. (1980). S-100-glia regulation of GABA transport across the nerve cell membrane.J. Neurol. Sci.45303–316. [DOI] [PubMed] [Google Scholar]
  8. Hyden, H., Cupello, A., and Palm, A. (1986).γ-Amino-butyric acid stimulates chloride permeability across microdissected Deiters' neuronal membrane.Brain Res.379167–170. [DOI] [PubMed] [Google Scholar]
  9. Hyden, H., Cupello, A., and Palm, A. (1987). GABAA receptor complexes are present on both sides of a GABA-acceptive neuronal membrane.Int. J. Neurosci.3719–26. [DOI] [PubMed] [Google Scholar]
  10. Jackson, M. B. (1989). Perfection of a synaptic receptor: Kinetics and energetics of the acetylcholine receptor.Proc. Natl. Acad. Sci. USA862199–2203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Krnjevic, K. (1981). Action of GABA on hippocampal neurons. InAmino Acid Neurotransmitters (F. V. De Feudis, and P. Mandel, eds.), Raven Press, New York, pp. 231–237. [PubMed] [Google Scholar]
  12. Krnjevic, K., and Schwartz, S. (1967). The action of theγ-amino-butyric acid on cortical neurons.Exp. Brain. Res.3320–336. [DOI] [PubMed] [Google Scholar]
  13. Llinas, R., Baker, R., and Precht, W. (1973). Blockage of inhibition by ammonium acetate action on chloride pump in cat trochlear motoneurons.J. Neurophys.37522–532. [DOI] [PubMed] [Google Scholar]
  14. Lux, H. D. (1971). Ammonium and chloride extrusion: hyperpolarizing synaptic inhibition in spinal motoneurons.Science173555–557. [DOI] [PubMed] [Google Scholar]
  15. Misgeld, U., Deisz, R. A., Dodt, H. U., and Lux, H. D. (1986). The role of chloride transport in post-synaptic inhibition of hippocampal neurons.Science2321413–1415. [DOI] [PubMed] [Google Scholar]
  16. Obata, K., Ito, M., Ochi, R., and Sato, N. (1967). Pharmacological properties of the post-synaptic inhibition by Purkinje cell axons and the action of GABA on Deiters' neuron.Exp. Brain Res.443–57. [DOI] [PubMed] [Google Scholar]
  17. Okada, Y., and Shimada, C. (1976).γ-amino-butyric acid (GABA) concentration in a single neuron-localization of GABA in Deiters' neuron.Brain Res.107658–662. [DOI] [PubMed] [Google Scholar]
  18. Olsen, R. W., Wong, E. H. F., Stauber, G. B., and King, R. G. (1984). Biochemical pharmacology of theγ-amino-butyric acid receptor/ionophore protein.Fed. Proc.432773–2778.6090223 [Google Scholar]
  19. Rapallino, M. V., Cupello, A., and Hydén, H. (1988a). GABAA receptors on the cytoplasmic side of the Deiters' neurone plasma membrane: Mechanism and functional implications.Int. J. Neurosci.4369–73. [DOI] [PubMed] [Google Scholar]
  20. Rapallino, M. V., Cupello, A., and Hydén, H. (1988b). Direct evidence for the presence of GABAA receptors on the cytoplasmic side of the Deiters' neurone membrane.Brain Res.462350–353. [DOI] [PubMed] [Google Scholar]
  21. Rapallino, M. V., Cupello, A., and Hydén, H. (1989). The mechanism by which intracellular GABA increases Cl− outward permeability across Deiters' neurone plasma membranes.Int. J. Neurosci.4571–74. [DOI] [PubMed] [Google Scholar]
  22. Rapallino, M. V., Cupello, A., and Hydén, H. (1990). Stimulation of36Cl− permeation in the in → out direction across the Deiters' neuron membrane by GABA on its cytoplasmic side: Effect of different ionic conditions.Int. J. Neurosci.53135–141. [DOI] [PubMed] [Google Scholar]
  23. Schofield, P. R., Darlison, M. G., Fujita, N., Burt, D. R., Stephenson, F. A., Rodriguez, H., Rhee, L. M., Ramachandran, J., Reale, V., 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.Nature328221–227. [DOI] [PubMed] [Google Scholar]

Articles from Cellular and Molecular Neurobiology are provided here courtesy of Springer

RESOURCES