Summary
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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References
Akaike, N., and Oomura, Y. (1984a). GABA-activated chloride channels in internally perfused frog dorsal root ganglion cells.Biomed. Res. 5115–132.
Akaike, N., and Oomura, Y. (1984b). GABA activates three types of the receptor-ionophore complex with their relative distribution.Soc. Neurosci. Abstr. 10643.
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.
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.
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.
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.
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.
Barker, J. L., and Mathers, D. A. (1981). GABA receptors and the depressant action of pentobarbital.Trends Neurosci. 410–13.
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.
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.
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.
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.
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.
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.
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.
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.
Curtis, D. R., and Johnston, G. A. R. (1974). Amino acid transmitters in the mammalian central nervous system.Ergebn. Physiol. 6997–118.
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.
Curtis, D. R., Lodge, D., Johnston, G. A. R., and Brand, S. J. (1976). Central actions of benzodiazepines.Brain Res. 118344–347.
Davis, J., and Watkins, J. C. (1974). The action ofβ-phenyl-GABA derivatives on neurones of the cat cerebral cortex.Brain Res. 70501–505.
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.
Dudel, J., and Finger, W. (1980). Closing of membrane channels effected byγ-aminobutyric acid (GABA) in crayfish muscle.Pflugers Arch. 387153–160.
Dudel, J., Finger, W., and Stettmeir, H. (1980). Inhibitory synaptic channels activated byγ-aminobutyric acid (GABA) in crayfish muscle.Pflugers Arch. 387143–151.
Evans, R. H. (1979). Potentiation of the effects of GABA by pentobarbitone.Brain Res. 171113–120.
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.
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.
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.
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.
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.
Higashi, H., and Nishi, S. (1982). Effect of barbiturates on the GABA receptor of cat primary afferent neurons.J. Physiol. (Lond.)332299–314.
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.
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.
Krespan, B., Springfield, S. A., Haas, H., and Geller, H. M. (1984). Electrophysiological studies on benzodiazepine antagonists.Brain Res. 295265–274.
Krogsgaard-Larsen, P., Johnston, G. A. R., Lodge, D., and Curtis, D. R. (1977). A new class of GABA agonist.Nature 26853–55.
Krnjević, K. (1974). Chemical nature of synaptic transmission in vertebrates.Physiol. Rev. 54419–540.
Levy, R. A. (1977). The role of GABA in primary afferent depolarization.Prog. Neurobiol. 19211–267.
MacDonald, R., and Barker, J. L. (1978). Benzodiazepines specifically modulate GABA-mediated postsynaptic inhibition in cultured mammalian neurones.Nature 271563–564.
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.
Nicoll, R. A. (1975). Presynaptic action of barbiturates in the frog spinal cord.Proc. Natl. Acad. Sci. 72 1460–1463.
Nishi, S., Minota, S., and Karczmar, A. G. (1974). Primary afferent neurones: The ionic mechanism of GABA-mediated depolarization.Neuropharmacology 13215–219.
Nistri, A., and Constanti, A. (1979). Pharmacological characterization of different types of GABA and glutamate receptors in vertebrates and invertebrates.Prog. Neurobiol. 13117–236.
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.
Olsen, R. W., and Snowman, A. M. (1982). Chloride-dependent enhancement by barbiturates ofγ-aminobutyric acid receptor binding.J. Neurosci. 21812–1823.
Olsen, R. W., and Snowman, A. M. (1985). Avermectin Bla modulation ofγ-aminobutyric acid/benzodiazepine receptor binding in mammalien brain.J. Neurochem. 441162–1168.
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.
Raabe, W., and Gumnit, R. J. (1977). Anticonvulsant action of diazepam: Increase of cortical postsynaptic inhibition.Epilepsia 18117–120.
Schlosser, W., and Franco, S. (1979). Reduction ofγ-aminobutyric acid (GABA)-mediated transmission by a convulsant benzodiazepine.J. Pharmacol. Exp. Ther. 211290–295.
Segal, M., and Barker, J. L. (1984). Rat hippocampal neurons in culture: Properties of GABA-activated Cl− ion conductance.J. Neurophysiol. 51500–515.
Simmonds, M. A. (1980). A site for the potentiation of GABA-mediated responses by benzodiazepines.Nature 284 558–560.
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.
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.
Takeuchi, A., and Takeuchi, N. (1965). Localized action of gamma-aminobutyric acid on crayfish muscle.J. Physiol. (Lond.)177225–238.
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.
Willow, M., and Johnston, G. A. R. (1980). Enhancement of GABA binding by pentobarbitone.Neurosci. Lett. 18323–327.
Willow, M., and Johnston, G. A. R. (1981a). Pentobarbitone slows the dissociation of GABA from rat brain synaptosomal binding sites.Neurosci. Lett. 2371–74.
Willow, M., and Johnston, G. A. R. (1981b). Dual action of pentobarbitone on GABA binding site integrity.J. Neurochem. 371291–1294.
Yarowski, P. J., and Carpenter, D. O. (1978). Receptors for gamma-amminobutyric acid (GABA) onAplysia neurons.Brain Res. 144:75–94.
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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
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DOI: https://doi.org/10.1007/BF00711116