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Chloride Channel Modulation at GABAergic Synapses in Primary Cultures of Cortical Neurons

  • Stefano Vicini
  • Jean Marc Mienville
  • Erminio Costa
Part of the Wenner-Gren Center International Symposium Series book series (WGCISS)

Abstract

The opening of Cl channels mediated by γ-aminobutyric acid (GABA) can be modulated by benzodiazepine (BZ) or beta-carboline (BC) recognition site ligands (Choi et al., 1977) which per se do not act on C1 channels. We studied these ligands at GABAergic synapses in primary cultures of rat cortical neurons and selected for this study flunitrazepam (a positive allosteric modulator) DMCM* (a negative allosteric modulator) and the imidazobenzodiazepine RO-151788** (a high affinity ligand with low intrinsic activity) (Hunkeler et al., 1981). Chan et al. (1985) have shown that flunitrazepam facilitates the Cl fluxes elicited by exogenous GABA in primary cultures of CNS neurons and DMCM decreases these ionic fluxes; moreover RO-151788 blocks the action of both compounds showing little or no intrinsic action. In the present study, the modulation of GABA mediated Cl channel opening was studied during the release of GABA from presynaptic endings at GABAergic synapses formed among rat cortical neurons in primary culture. The direct action of these three compounds on Cl channel was also studied in membrane patches excised from these neurons. This study was intended to further understanding of the physiological role of the allosteric modulation of GABA recognition sites by exogenous and endogenous ligands of BZ-BC recognition sites.

Keywords

Synaptic Current Membrane Patch Decay Time Constant GABAergic Synapse Positive Allosteric Modulator 
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.

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References

  1. Bormann, J. and Clapham, D.E. (1985). Y-Aminobutyric acid receptor channels in adrenal chromaffin cells: A patch-clamp study. Proc. Natl. Acad. Sci. USA 82, 2168–2172.CrossRefGoogle Scholar
  2. Hamill, O.P., Marty, A., Neher, E., Sakmann, B. and Sigworth, F.J. (1981). Improved patch-clamp techniques for high resolution current recording from cells and cell-free membrane patches. Pfluger Arch. 391, 85–100.CrossRefGoogle Scholar
  3. Chan, C.Y. and Farb, D.H. (1985). Modulation of neurotransmitter action: Control of the T-aminobutyric acid response through the benzodiazepine receptor. J. Neurosci. 5, 2365–2373.Google Scholar
  4. Choi, D.W., Farb, D.H. and Fishbach, G.D. (1977). Chlordiazepoxide selectively augments GABA action in spinal cord cell cultures. Nature 269, 342–344.CrossRefGoogle Scholar
  5. Hunkeler, W., Mohler, H., Pieri, L., Polo, P., Bonetti, E.P., Cumin, R., Schaffner, R. and Haefely, W. (1981). Selective antagonists of benzodiazepines. Nature 290, 514–516.CrossRefGoogle Scholar
  6. Johnston, D. and Brown, T.H. (1983). Interpretation of voltage-clamp measurements in hippocampal neurons. J. Neurophysiol. 50, 464–486.Google Scholar
  7. Middleton, P., Jaramillo, F. and Schuetze S.M. (1986). Forskolin increase the rate of acetylcholine receptor desensitization at rat soleus end plates. Proc. Natl. Acad. Sci. USA, 83, 4967–4971.CrossRefGoogle Scholar
  8. Vicini, S., Alho, H., Costa, E., Mienville, J.M., Santi, M.R. and Vaccarino, F.M. (1986). Modulation of 7-aminobutyric acid mediated inhibitory synaptic currents in dissociated cortical cell cultures. Proc. Natl. Acad. Sci. USA, in press.Google Scholar

Copyright information

© The Wenner-Gren Center 1987

Authors and Affiliations

  • Stefano Vicini
  • Jean Marc Mienville
  • Erminio Costa

There are no affiliations available

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