Skip to main content
PMC home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1981 Nov;78(11):7180–7184. doi: 10.1073/pnas.78.11.7180

Diazepam and (--)-pentobarbital: fluctuation analysis reveals different mechanisms for potentiation of gamma-aminobutyric acid responses in cultured central neurons.

R E Study, J L Barker
PMCID: PMC349220  PMID: 6273918

Abstract

Diazepam and (--)-pentobarbital each potentiate the increase in chloride ion conductance produced by gamma-aminobutyric acid (GABA) i voltage-clamped mouse spinal neurons grown in culture. Fluctuation analysis was used to compare the properties of elementary ion-channel events underlying the chloride conductance produced by GABA alone and during potentiation by the two drugs. Neither drug altered the conductance of an open ion channel, but both drugs affected the kinetics of channel activity. Diazepam increased the frequency of channel openings and either did not affect or slightly increased the average open-channel lifetime, whereas (--)-pentobarbital decreased the frequency of channel openings and increased average open-channel lifetime. These changes in the kinetics of GABA-activated ion channels can quantitatively account for the potentiation of GABA responses observed with the drugs. Thus, the drugs each increase the response to GABA but do not act on channel kinetics in the same manner.

Full text

PDF
7180

Images in this article

7181Image
on p.7181

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Anderson C. R., Stevens C. F. Voltage clamp analysis of acetylcholine produced end-plate current fluctuations at frog neuromuscular junction. J Physiol. 1973 Dec;235(3):655–691. doi: 10.1113/jphysiol.1973.sp010410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Ascher P., Large W. A., Rang H. P. Studies on the mechanism of action of acetylcholine antagonists on rat parasympathetic ganglion cells. J Physiol. 1979 Oct;295:139–170. doi: 10.1113/jphysiol.1979.sp012958. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Ascher P., Marty A., Neild T. O. Life time and elementary conductance of the channels mediating the excitatory effects of acetylcholine in Aplysia neurones. J Physiol. 1978 May;278:177–206. doi: 10.1113/jphysiol.1978.sp012299. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Barker J. L., McBurney R. N. Phenobarbitone modulation of postsynaptic GABA receptor function on cultured mammalian neurons. Proc R Soc Lond B Biol Sci. 1979 Dec 31;206(1164):319–327. doi: 10.1098/rspb.1979.0108. [DOI] [PubMed] [Google Scholar]
  5. Barker J. L., Ransom B. R. Amino acid pharmacology of mammalian central neurones grown in tissue culture. J Physiol. 1978 Jul;280:331–354. doi: 10.1113/jphysiol.1978.sp012387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Barker J. L., Ransom B. R. Pentobarbitone pharmacology of mammalian central neurones grown in tissue culture. J Physiol. 1978 Jul;280:355–372. doi: 10.1113/jphysiol.1978.sp012388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Choi D. W., Farb D. H., Fischbach G. D. Chlordiazepoxide selectively potentiates GABA conductance of spinal cord and sensory neurons in cell culture. J Neurophysiol. 1981 Apr;45(4):621–631. doi: 10.1152/jn.1981.45.4.621. [DOI] [PubMed] [Google Scholar]
  8. Costa E., Guidotti A. Molecular mechanisms in the receptor action of benzodiazepines. Annu Rev Pharmacol Toxicol. 1979;19:531–545. doi: 10.1146/annurev.pa.19.040179.002531. [DOI] [PubMed] [Google Scholar]
  9. DeFelice L. J. Fluctuation analysis in neurobiology. Int Rev Neurobiol. 1977;20:169–208. doi: 10.1016/s0074-7742(08)60653-4. [DOI] [PubMed] [Google Scholar]
  10. Dudel J., Finger W., Stettmeier H. Inhibitory synaptic channels activated by gamma-aminobutyric acid (GABA) in crayfish muscle. Pflugers Arch. 1980 Sep;387(2):143–151. doi: 10.1007/BF00584265. [DOI] [PubMed] [Google Scholar]
  11. ECCLES J. C., SCHMIDT R., WILLIS W. D. PHARMACOLOGICAL STUDIES ON PRESYNAPTIC INHIBITION. J Physiol. 1963 Oct;168:500–530. doi: 10.1113/jphysiol.1963.sp007205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Faber D. S., Korn H. Single-shot channel activation accounts for duration of inhibitory postsynaptic potentials in a central neuron. Science. 1980 May 9;208(4444):612–615. doi: 10.1126/science.6245449. [DOI] [PubMed] [Google Scholar]
  13. Huang L. Y., Barker J. L. Pentobarbital: stereospecific actions of (+) and (-) isomers revealed on cultured mammalian neurons. Science. 1980 Jan 11;207(4427):195–197. doi: 10.1126/science.7350656. [DOI] [PubMed] [Google Scholar]
  14. MacDermott A. B., Connor E. A., Dionne V. E., Parsons R. L. Voltage clamp study of fast excitatory synaptic currents in bullfrog sympathetic ganglion cells. J Gen Physiol. 1980 Jan;75(1):39–60. doi: 10.1085/jgp.75.1.39. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. MacDonald R. L., Barker J. L. Enhancement of GABA-mediated postsynaptic inhibition in cultured mammalian spinal cord neurons: a common mode of anticonvulsant action. Brain Res. 1979 May 11;167(2):323–336. doi: 10.1016/0006-8993(79)90826-6. [DOI] [PubMed] [Google Scholar]
  16. Macdonald R., Barker J. L. Benzodiazepines specifically modulate GABA-mediated postsynaptic inhibition in cultured mammalian neurones. Nature. 1978 Feb 9;271(5645):563–564. doi: 10.1038/271563a0. [DOI] [PubMed] [Google Scholar]
  17. McBurney R. N., Barker J. L. GABA-induced conductance fluctuations in cultured spinal neurones. Nature. 1978 Aug 10;274(5671):596–597. doi: 10.1038/274596a0. [DOI] [PubMed] [Google Scholar]
  18. Neher E., Stevens C. F. Conductance fluctuations and ionic pores in membranes. Annu Rev Biophys Bioeng. 1977;6:345–381. doi: 10.1146/annurev.bb.06.060177.002021. [DOI] [PubMed] [Google Scholar]
  19. Nicoll R. A. Pentobarbital: action on frog motoneurons. Brain Res. 1975 Oct 10;96(1):119–123. doi: 10.1016/0006-8993(75)90582-x. [DOI] [PubMed] [Google Scholar]
  20. Ransom B. R., Barker J. L. Pentobarbital modulates transmitter effects on mouse spinal neurones grown in tissue culture. Nature. 1975 Apr 24;254(5502):703–705. doi: 10.1038/254703a0. [DOI] [PubMed] [Google Scholar]
  21. Ransom B. R., Neale E., Henkart M., Bullock P. N., Nelson P. G. Mouse spinal cord in cell culture. I. Morphology and intrinsic neuronal electrophysiologic properties. J Neurophysiol. 1977 Sep;40(5):1132–1150. doi: 10.1152/jn.1977.40.5.1132. [DOI] [PubMed] [Google Scholar]
  22. Willow M., Johnston G. A. Enhancement of GABA binding by pentobarbitone. Neurosci Lett. 1980 Jul;18(3):323–327. doi: 10.1016/0304-3940(80)90305-5. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES