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. 1973 May;48(1):1–11. doi: 10.1111/j.1476-5381.1973.tb08216.x

A method for comparing the potencies of γ-aminobutyric acid antagonists on single cortical neurones using micro-iontophoretic techniques

R G Hill, M A Simmonds
PMCID: PMC1776088  PMID: 4724192

Abstract

1. By the use of micro-iontophoretic techniques, quantitative estimates of the depressant effect of γ-aminobutyric acid (GABA) have been obtained from single neurones in the middle suprasylvian gyrus of cat cerebral cortex.

2. The progressive reduction in firing rate of the neurone during each microiontophoretic application of GABA was followed until inhibition was complete. The resultant time-response curves represented cumulative concentration-response relationships which could be characterized by measuring the time taken to achieve 50% inhibition (T50) of neuronal firing.

3. The time-response curves for GABA could be displaced along the time axis by micro-iontophoretic application of picrotoxin, bicuculline or strychnine. A displaced curve was more nearly parallel to the control curve when responses were plotted against linear rather than log time.

4. Picrotoxin usually increased T50 values for GABA, bicuculline could both increase and decrease them and strychnine usually decreased them.

5. When displacements of GABA response curves were expressed as difference between T50 (test-control)/T50 (control), the values obtained were minimally influenced by the size of the current applying GABA and were unaffected by changes in the retaining current passed through the GABA barrel between applications.

6. The use of this method to compare the micro-iontophoretic potencies of different GABA antagonists is discussed.

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Selected References

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

  1. Beart P. M., Johnston G. A. Bicuculline and GABA-metabolising enzymes. Brain Res. 1972 Mar 10;38(1):226–227. doi: 10.1016/0006-8993(72)90609-9. [DOI] [PubMed] [Google Scholar]
  2. Bradley P. B., Candy J. M. Iontophoretic release of acetylcholine, noradrenaline, 5-hydroxytryptamine and D-lysergic acid diethylamide from micropipettes. Br J Pharmacol. 1970 Oct;40(2):194–201. doi: 10.1111/j.1476-5381.1970.tb09913.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Clarke G., Hill R. G., Simmonds M. A. Microiontophoretic release of drugs from micropipettes: use of 24Na as a model. Br J Pharmacol. 1973 May;48(1):156–161. doi: 10.1111/j.1476-5381.1973.tb08234.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Curtis D. R., Duggan A. W., Johnston G. A. The specificity of strychnine as a glycine antagonist in the mammalian spinal cord. Exp Brain Res. 1971 Jun 29;12(5):547–565. doi: 10.1007/BF00234248. [DOI] [PubMed] [Google Scholar]
  5. Cuthbert A. W., Dunant Y. Diffusion of drugs through stationary water layers as the rate limiting process in their action at membrane receptors. Br J Pharmacol. 1970 Nov;40(3):508–521. doi: 10.1111/j.1476-5381.1970.tb10632.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DEL CASTILLO L., KATZ B. A study of curare action with an electrical micromethod. Proc R Soc Lond B Biol Sci. 1957 May 7;146(924):339–356. doi: 10.1098/rspb.1957.0015. [DOI] [PubMed] [Google Scholar]
  7. Engberg I., Thaller A. On the interaction of picrotoxin with GABA and glycine in the spinal cord. Brain Res. 1970 Apr 1;19(1):151–154. doi: 10.1016/0006-8993(70)90244-1. [DOI] [PubMed] [Google Scholar]
  8. Godfraind J. M., Krnjević K., Pumain R. Doubtful value of bicuculline as a specific antagonist of GABA. Nature. 1970 Nov 14;228(5272):675–676. doi: 10.1038/228675a0. [DOI] [PubMed] [Google Scholar]
  9. Hill R. G., Simmonds M. A., Straughan D. W. Antagonism of GABA by picrotoxin in the feline cerebral cortex. Br J Pharmacol. 1972 Apr;44(4):807–809. doi: 10.1111/j.1476-5381.1972.tb07319.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Hoffer B. J., Neff N. H., Siggins G. R. Microiontophoretic release of norepinephrine from micropipettes. Neuropharmacology. 1971 Mar;10(21):175–180. doi: 10.1016/0028-3908(71)90038-4. [DOI] [PubMed] [Google Scholar]
  11. Iversen L. L., Johnston G. A. GABA uptake in rat central nervous system: comparison of uptake in slices and homogenates and the effects of some inhibitors. J Neurochem. 1971 Oct;18(10):1939–1950. doi: 10.1111/j.1471-4159.1971.tb09600.x. [DOI] [PubMed] [Google Scholar]
  12. Johnson E. S., Roberts M. H., Straughan D. W. Amino-acid induced depression of cortical neurones. Br J Pharmacol. 1970 Apr;38(4):659–666. doi: 10.1111/j.1476-5381.1970.tb09875.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Obata K., Takeda K., Shinozaki H. Electrophoretic release of gamma-aminobutyric acid and glutamic acid from micropipettes. Neuropharmacology. 1970 May;9(3):191–194. doi: 10.1016/0028-3908(70)90066-3. [DOI] [PubMed] [Google Scholar]
  14. Obata K., Takeda K., Shinozaki H. Further study on pharmacological properties of the cerebellar-induced inhibition of deiters neurones. Exp Brain Res. 1970 Nov 26;11(4):327–342. doi: 10.1007/BF00237907. [DOI] [PubMed] [Google Scholar]
  15. STEPHENSON R. P. A modification of receptor theory. Br J Pharmacol Chemother. 1956 Dec;11(4):379–393. doi: 10.1111/j.1476-5381.1956.tb00006.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Straughan D. W., Neal M. J., Simmonds M. A., Collins G. G., Hill R. G. Evaluation of bicuculline as a GABA antagonist. Nature. 1971 Oct 1;233(5318):352–354. doi: 10.1038/233352a0. [DOI] [PubMed] [Google Scholar]
  17. ten Bruggencate G., Engberg I. Iontophoretic studies in Deiters' nucleus of the inhibitory actions of GABA and related amino acids and the interactions of strychnine and picrotoxin. Brain Res. 1971 Feb 5;25(3):431–448. doi: 10.1016/0006-8993(71)90453-7. [DOI] [PubMed] [Google Scholar]

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