Skip to main content
SpringerLink
Log in

Diazepam action onγ-aminobutyric acid-activated chloride currents in internally perfused frog sensory neurons

  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Summary

  1. 1.

    The Cl− current (I Cl) inγ-aminobutyric acid (GABA)-sensitive frog sensory neuron was separated from other Na+, Ca2+, and K+ currents using a suction pipette technique which allows internal perfusion under a single-electrode voltage clamp.

  2. 2.

    Diazepam (DZP) itself evoked no response but facilitated the dose- and time-dependently GABA-inducedI Cl without changing the GABA equilibrium potential (E GABA) at concentrations ranging widely, from 3 × 10−9 to 10−4 M.

  3. 3.

    In the presence of DZP, the GABA dose-response curve shifted to the left without changing the maximum current, indicating that DZP modifies the interaction between GABA and its receptor rather than affecting directly the channel activation step.

  4. 4.

    The enhancement of the GABA-inducedI Cl by DZP depended neither on the membrane voltage nor on the inward or outward direction of theI Cl.

  5. 5.

    DZP also potentiated theI Cl elicited by GABA agonists such asβ-alanine, taurine, homotaurine, 5-aminovaleric acid,l-GABOB,d-GABOB, glycine, and muscimol.

  6. 6.

    The GABA response enhanced by pentobarbital (PB) was further enhanced by adding DZP, indicating that DZP and PB do not act in the same way.

  7. 7.

    Ro5-3663, a diazepam analogue, enhanced the GABA-inducedI Cl only in a narrow range of the concentrations but inhibited the current at concentrations higher than 2 × 10−6 M.

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

  • Akaike, N., and Oomura, Y. (1984a). GABA-activated chloride channels in internally perfused frog dorsal root ganglion cells.Biomed. Res. 5115–132.

    Google Scholar 

  • Akaike, N., and Oomura, Y. (1984b). GABA activates three types of the receptor-ionophore complex with their relative distribution.Soc. Neurosci. Abstr. 10643.

    Google Scholar 

  • Akaike, N., Hattori, K., Inomata, N., and Oomura, Y. (1985a).γ-Aminobutyric acid and pentobarbitone gated chloride currents in internally perfused frog sensory neurones.J. Physiol. (Lond.)360367–386.

    Google Scholar 

  • Akaike, N., Hattori, K., Oomura, Y., and Carpenter, D. O. (1985b). Bicucullin and picrotoxin blockγ-aminobutyric acid-gated Cl− conductance by different mechanisms.Experientia 4170–71.

    Google Scholar 

  • Akaike, N., Inoue, M., and Krishtal, O. A. (1986). “Concentration clamp” study ofγ-aminobutyric acidinduced chloride current kinetics in frog sensory neurones.J. Physiol. (Lond.) (in press).

  • Alger, B. E., and Nicoll, R. A. (1979). GABA-mediated biphasic inhibitory responses in hippocampus.Nature 281315–317.

    Google Scholar 

  • Alger, B. E., and Nicoll, R. A. (1982). Pharmacological evidence for two kinds of GABA receptor on rat hippocampal pyramidal cells studiedin vitro.J. Physiol. (Lond.)32825–141.

    Google Scholar 

  • Andersen, P., Dingledine, R., Gjerstad, L., Langmoen, I. A., and Laursen, A. (1980). Two different responses of hippocampal pyramical cells to application of gamma-aminobutyric acid.J. Physiol. (Lond.)305 279–295.

    Google Scholar 

  • Barker, J. L., and Mathers, D. A. (1981). GABA receptors and the depressant action of pentobarbital.Trends Neurosci. 410–13.

    Google Scholar 

  • Barker, J. L., McBurney, R. N., and MacDonald, J. F. (1982). Fluctuation analysis of neutral amino acid responses in cultured mouse spinal neurones.J. Physiol. (Lond.)322365–388.

    Google Scholar 

  • Bowery, N. G., Doble, A., Hill, D. R., Hudson, A. L., Shaw, J., and Turnbull, M. J. (1980).β-Chlorophenyl GABA (Baclofen) is a selective ligand for a novel GABA receptor on nerve terminals.Brain Res. Bull. 5 497–502.

    Google Scholar 

  • Brown, D. A., and Galvan, M. (1977). Influence of neuroglial transport on action ofγ-aminobutyric acid on mammalian ganglion cells.Br. J. Pharmacol. 59373–378.

    Google Scholar 

  • Chan, C. Y., and Farb, D. H. (1985). Modulation of neurotransmitter action: Control of theγ-aminobutyric acid response through the benzodiazepine receptor.J. Neurosci. 52365–2373.

    Google Scholar 

  • Chan, C. Y., Gibbs, T. T., Borden, L. A., and Farb, D. H. (1983). Multiple embryonic benzodiazepine binding sites: Evidence for functionality.Life Sci. 332061–2069.

    Google Scholar 

  • Choi, D. W., Farb, D. H., and Fischbach, G. D. (1981a). Chlordiazepoxide selectively potentiates GABA conductance of spinal cord and sensory neurones in cell culture.J. Neurophysiol. 45620–631.

    Google Scholar 

  • Choi, D. W., Farb, D. H., and Fischbach, G. D. (1981b). GABA-mediated synaptic potentials in chick spinal cord and sensory neurons. J. Neurophysiol.45632–643.

    Google Scholar 

  • Connors, B. W. (1981). A comparison of the effect of pentobarbital and diphenylhydantoin on the GABA sensitivity and excitability of adult sensory ganglion cells.Brain Res. 207357–369.

    Google Scholar 

  • Curtis, D. R., and Johnston, G. A. R. (1974). Amino acid transmitters in the mammalian central nervous system.Ergebn. Physiol. 6997–118.

    Google Scholar 

  • Curtis, D. R., Game, C. J. A., Johnston, G. A. R., and McCulloch, R. M. (1974). Central effects ofβ-(pchlorophenyl)-γ-aminobutyric acid.Brain Res. 70493–499.

    Google Scholar 

  • Curtis, D. R., Lodge, D., Johnston, G. A. R., and Brand, S. J. (1976). Central actions of benzodiazepines.Brain Res. 118344–347.

    Google Scholar 

  • Davis, J., and Watkins, J. C. (1974). The action ofβ-phenyl-GABA derivatives on neurones of the cat cerebral cortex.Brain Res. 70501–505.

    Google Scholar 

  • Desarmenien, M., Feltz, P., and Headley, P. M. (1980). Does glial uptake affect GABA responses? An intracellular study on rat dorsal root ganglion neuronsin vitro.J. Physiol. (Lond.)307163–182.

    Google Scholar 

  • Dudel, J., and Finger, W. (1980). Closing of membrane channels effected byγ-aminobutyric acid (GABA) in crayfish muscle.Pflugers Arch. 387153–160.

    Google Scholar 

  • Dudel, J., Finger, W., and Stettmeir, H. (1980). Inhibitory synaptic channels activated byγ-aminobutyric acid (GABA) in crayfish muscle.Pflugers Arch. 387143–151.

    Google Scholar 

  • Evans, R. H. (1979). Potentiation of the effects of GABA by pentobarbitone.Brain Res. 171113–120.

    Google Scholar 

  • Feltz, P., and Rasminsky, M. (1974). A model for the mode of action of GABA on primary afferent terminals: Depolarizing effects of GABA applied iontophoretically to neurons of mammalian dorsal root ganglion.Neuropharmacology 13 533–563.

    Google Scholar 

  • Gallagher, J. P., Higashi, H., and Nishi, S. (1978). Characterization and ionic basis of GABA-induced depolarizations recordedin vitro from cat primary afferent neurones.J. Physiol. (Lond.)275263–282.

    Google Scholar 

  • Gallagher, J. P., Nakamura, J., and Shinnick-Gallagher, P. (1983). Effect of glial uptake and desensitization on the activity ofγ-aminobutyric acid (GABA) and its analogs at the cat dorsal root ganglion.J. Pharmacol. Exp. Ther. 226876–884.

    Google Scholar 

  • Hattori, K., Akaike, N., Oomura, Y., and Kuraoka, S. (1984). Internal perfusion studies to demonstrate GABA-induced chloride responses in the frog primary afferent neurons.Am. J. Physiol. 246C259–265.

    Google Scholar 

  • Headley, P. M., Desarmenien, M., Santangelo, F., and Feltz, P. (1981). Direct action of pentobarbitone in potentiating the responses to GABA of rat dorsal root ganglion neurons in vitro.Neurosci. Let. 24273–278.

    Google Scholar 

  • Higashi, H., and Nishi, S. (1982). Effect of barbiturates on the GABA receptor of cat primary afferent neurons.J. Physiol. (Lond.)332299–314.

    Google Scholar 

  • Ishizuka, S., Hattori, K., and Akaike, N. (1984). Separation of ionic currents in the somatic membrane of frog sensory neurons.J. Membr. Biol. 7819–28.

    Google Scholar 

  • Kiskin, N. I., Krishtal, O. A., and Tsyndrenko, A. Ya (1986). Excitatory amino acid receptors in hippocampal neurones: Kainate fails to desensitize them.Neurosci. Lett. 63225–230.

    Google Scholar 

  • Krespan, B., Springfield, S. A., Haas, H., and Geller, H. M. (1984). Electrophysiological studies on benzodiazepine antagonists.Brain Res. 295265–274.

    Google Scholar 

  • Krogsgaard-Larsen, P., Johnston, G. A. R., Lodge, D., and Curtis, D. R. (1977). A new class of GABA agonist.Nature 26853–55.

    Google Scholar 

  • Krnjević, K. (1974). Chemical nature of synaptic transmission in vertebrates.Physiol. Rev. 54419–540.

    Google Scholar 

  • Levy, R. A. (1977). The role of GABA in primary afferent depolarization.Prog. Neurobiol. 19211–267.

    Google Scholar 

  • MacDonald, R., and Barker, J. L. (1978). Benzodiazepines specifically modulate GABA-mediated postsynaptic inhibition in cultured mammalian neurones.Nature 271563–564.

    Google Scholar 

  • Mayer, M. L., Higashi, H., Gallagher, J. P., and Shinnick-Gallagher, P. (1983). On the mechanism of action of GABA in pelvic vesical ganglia: Biphasic responses evoked by two opposing actions on membrane conductance.Brain Res. 260233–248.

    Google Scholar 

  • Nicoll, R. A. (1975). Presynaptic action of barbiturates in the frog spinal cord.Proc. Natl. Acad. Sci. 72 1460–1463.

    Google Scholar 

  • Nishi, S., Minota, S., and Karczmar, A. G. (1974). Primary afferent neurones: The ionic mechanism of GABA-mediated depolarization.Neuropharmacology 13215–219.

    Google Scholar 

  • Nistri, A., and Constanti, A. (1979). Pharmacological characterization of different types of GABA and glutamate receptors in vertebrates and invertebrates.Prog. Neurobiol. 13117–236.

    Google Scholar 

  • Olsen, R. W., and Leeb-Lundberg, F. (1981). Convulsant and anticonvulsant drug binding sites related to GABA-regulated chloride ion channels. InAdvances in Biochemical Psychopharmacology (Costa, E., Di Chiara, G., and Gessa, G. L., Eds.), Raven Press, New York, Vol. 26, pp. 93–102.

    Google Scholar 

  • Olsen, R. W., and Snowman, A. M. (1982). Chloride-dependent enhancement by barbiturates ofγ-aminobutyric acid receptor binding.J. Neurosci. 21812–1823.

    Google Scholar 

  • Olsen, R. W., and Snowman, A. M. (1985). Avermectin Bla modulation ofγ-aminobutyric acid/benzodiazepine receptor binding in mammalien brain.J. Neurochem. 441162–1168.

    Google Scholar 

  • Padjen, A. L., and Hashiguchi, T. (1983). Primary afferent depolarization in frog spinal cord is associated with an increase in membrane conductance.Can. J. Physiol. Pharmacol. 60626–631.

    Google Scholar 

  • Raabe, W., and Gumnit, R. J. (1977). Anticonvulsant action of diazepam: Increase of cortical postsynaptic inhibition.Epilepsia 18117–120.

    Google Scholar 

  • Schlosser, W., and Franco, S. (1979). Reduction ofγ-aminobutyric acid (GABA)-mediated transmission by a convulsant benzodiazepine.J. Pharmacol. Exp. Ther. 211290–295.

    Google Scholar 

  • Segal, M., and Barker, J. L. (1984). Rat hippocampal neurons in culture: Properties of GABA-activated Cl− ion conductance.J. Neurophysiol. 51500–515.

    Google Scholar 

  • Simmonds, M. A. (1980). A site for the potentiation of GABA-mediated responses by benzodiazepines.Nature 284 558–560.

    Google Scholar 

  • Skerritt, J. H., and MacDonald, R. L. (1984). Benzodiazepine receptor ligand actions on GABA responses. Benzodiazepines, CL 218872, zopiclone.Eur. J. Pharm. 101 127–134.

    Google Scholar 

  • Suria, A., and Costa, E. (1975). Action of diazepam, dibutyl cGMP, and GABA on presynaptic nerve terminals in bullfrog sympathetic ganglia.Brain Res. 87102–106.

    Google Scholar 

  • Takeuchi, A., and Takeuchi, N. (1965). Localized action of gamma-aminobutyric acid on crayfish muscle.J. Physiol. (Lond.)177225–238.

    Google Scholar 

  • White, W. F., Dichter, M. A., and Snodgrass, S. R. (1981). Benzodiazepine binding and interactions with the GABA receptor complex in living cultures of rat cerebral cortex.Brain Res. 215162–176.

    Google Scholar 

  • Willow, M., and Johnston, G. A. R. (1980). Enhancement of GABA binding by pentobarbitone.Neurosci. Lett. 18323–327.

    Google Scholar 

  • Willow, M., and Johnston, G. A. R. (1981a). Pentobarbitone slows the dissociation of GABA from rat brain synaptosomal binding sites.Neurosci. Lett. 2371–74.

    Google Scholar 

  • Willow, M., and Johnston, G. A. R. (1981b). Dual action of pentobarbitone on GABA binding site integrity.J. Neurochem. 371291–1294.

    Google Scholar 

  • Yarowski, P. J., and Carpenter, D. O. (1978). Receptors for gamma-amminobutyric acid (GABA) onAplysia neurons.Brain Res. 144:75–94.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Physiology, Faculty of Medicine, Kyushu University 60, 812, Fukuoka, Japan

    Kiichi Hattori, Yutaka Oomura & Norio Akaike

Authors
  1. Kiichi Hattori
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yutaka Oomura
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Norio Akaike
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hattori, K., Oomura, Y. & Akaike, N. Diazepam action onγ-aminobutyric acid-activated chloride currents in internally perfused frog sensory neurons. Cell Mol Neurobiol 6, 307–323 (1986). https://doi.org/10.1007/BF00711116

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00711116

Key words

Search

Navigation