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. 1991;440:67–83. doi: 10.1113/jphysiol.1991.sp018696

Strychnine-sensitive glycine responses of neonatal rat hippocampal neurones.

S Ito 1, E Cherubini 1
PMCID: PMC1180140  PMID: 1804982

Abstract

1. Intracellular recordings employing current and voltage clamp techniques were used to study the effects of glycine on rat CA3 hippocampal neurones during the first 3 weeks of postnatal (P) life. 2. Glycine (0.3-1 mM) depolarized neurones from rats less than 4 days old (P4). Neurones from older neonates (P5-P7) were hyperpolarized by glycine, whereas adult neurones were unaffected. 3. Both depolarizing and hyperpolarizing responses were associated with large conductance increases; they reversed polarity at a potential which changed with the extracellular chloride concentration. The responses persisted in tetrodotoxin (1 microM) or in a solution with a much reduced calcium concentration. 4. Strychnine (1 microM) but not bicuculline (10-50 microM) antagonized the effects of glycine. The action of strychnine was apparently competitive with a dissociation constant of 350 nM. 5. In voltage clamp experiments, glycine elicited a non-desensitizing outward current at -60 mV. When a maximal concentration of glycine was applied at the same time as gamma-aminobutyric acid (GABA), the conductance increase induced by the two agonists was additive, suggesting the activation of different populations of channels. 6. Concentrations of glycine lower than 100 microM did not affect membrane potential. However, at 30-50 microM glycine increased the frequency of spontaneous GABA-mediated synaptic responses; this action was not blocked by strychnine. 7. It is concluded that during the first 2 weeks of life glycine acts at strychnine-sensitive receptors to open chloride channels.

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Selected References

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  1. ARAKI T., ITO M., OSCARSSON O. Anion permeability of the synaptic and non-synaptic motoneurone membrane. J Physiol. 1961 Dec;159:410–435. doi: 10.1113/jphysiol.1961.sp006818. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Adams P. R., Constanti A., Banks F. W. Voltage clamp analysis of inhibitory synaptic action in crayfish stretch receptor neurons. Fed Proc. 1981 Sep;40(11):2637–2641. [PubMed] [Google Scholar]
  3. Akagi H., Miledi R. Heterogeneity of glycine receptors and their messenger RNAs in rat brain and spinal cord. Science. 1988 Oct 14;242(4876):270–273. doi: 10.1126/science.2845580. [DOI] [PubMed] [Google Scholar]
  4. Akaike N., Kaneda M. Glycine-gated chloride current in acutely isolated rat hypothalamic neurons. J Neurophysiol. 1989 Dec;62(6):1400–1409. doi: 10.1152/jn.1989.62.6.1400. [DOI] [PubMed] [Google Scholar]
  5. Barker J. L., McBurney R. N. GABA and glycine may share the same conductance channel on cultured mammalian neurones. Nature. 1979 Jan 18;277(5693):234–236. doi: 10.1038/277234a0. [DOI] [PubMed] [Google Scholar]
  6. Barker J. L., McBurney R. N., MacDonald J. F. Fluctuation analysis of neutral amino acid responses in cultured mouse spinal neurones. J Physiol. 1982 Jan;322:365–387. doi: 10.1113/jphysiol.1982.sp014042. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Becker C. M., Hoch W., Betz H. Glycine receptor heterogeneity in rat spinal cord during postnatal development. EMBO J. 1988 Dec 1;7(12):3717–3726. doi: 10.1002/j.1460-2075.1988.tb03255.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ben-Ari Y., Cherubini E., Corradetti R., Gaiarsa J. L. Giant synaptic potentials in immature rat CA3 hippocampal neurones. J Physiol. 1989 Sep;416:303–325. doi: 10.1113/jphysiol.1989.sp017762. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Ben-Ari Y., Krnjević K., Reiffenstein R. J., Reinhardt W. Inhibitory conductance changes and action of gamma-aminobutyrate in rat hippocampus. Neuroscience. 1981;6(12):2445–2463. doi: 10.1016/0306-4522(81)90091-9. [DOI] [PubMed] [Google Scholar]
  10. Benavides J., López-Lahoya J., Valdivieso F., Ugarte M. Postnatal development of synaptic glycine receptors in normal and hyperglycinemic rats. J Neurochem. 1981 Aug;37(2):315–320. doi: 10.1111/j.1471-4159.1981.tb00457.x. [DOI] [PubMed] [Google Scholar]
  11. Bormann J., Hamill O. P., Sakmann B. Mechanism of anion permeation through channels gated by glycine and gamma-aminobutyric acid in mouse cultured spinal neurones. J Physiol. 1987 Apr;385:243–286. doi: 10.1113/jphysiol.1987.sp016493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Bristow D. R., Bowery N. G., Woodruff G. N. Light microscopic autoradiographic localisation of [3H]glycine and [3H]strychnine binding sites in rat brain. Eur J Pharmacol. 1986 Jul 31;126(3):303–307. doi: 10.1016/0014-2999(86)90062-2. [DOI] [PubMed] [Google Scholar]
  13. Brüning G., Bauer R., Baumgarten H. G. Postnatal development of [3H]flunitrazepam and [3H]strychnine binding sites in rat spinal cord localized by quantitative autoradiography. Neurosci Lett. 1990 Mar 2;110(1-2):6–10. doi: 10.1016/0304-3940(90)90778-8. [DOI] [PubMed] [Google Scholar]
  14. COOMBS J. S., ECCLES J. C., FATT P. The specific ionic conductances and the ionic movements across the motoneuronal membrane that produce the inhibitory post-synaptic potential. J Physiol. 1955 Nov 28;130(2):326–374. doi: 10.1113/jphysiol.1955.sp005412. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Curtis D. R., Hösli L., Johnston G. A., Johnston I. H. The hyperpolarization of spinal motoneurones by glycine and related amino acids. Exp Brain Res. 1968;5(3):235–258. doi: 10.1007/BF00238666. [DOI] [PubMed] [Google Scholar]
  16. Gaiarsa J. L., Corradetti R., Cherubini E., Ben-Ari Y. The allosteric glycine site of the N-methyl-D-aspartate receptor modulates GABAergic-mediated synaptic events in neonatal rat CA3 hippocampal neurons. Proc Natl Acad Sci U S A. 1990 Jan;87(1):343–346. doi: 10.1073/pnas.87.1.343. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Gold M. R., Martin A. R. gamma-Aminobutyric acid and glycine activate Cl- channels having different characteristics in CNS neurones. Nature. 1984 Apr 12;308(5960):639–641. doi: 10.1038/308639a0. [DOI] [PubMed] [Google Scholar]
  18. Grenningloh G., Rienitz A., Schmitt B., Methfessel C., Zensen M., Beyreuther K., Gundelfinger E. D., Betz H. The strychnine-binding subunit of the glycine receptor shows homology with nicotinic acetylcholine receptors. Nature. 1987 Jul 16;328(6127):215–220. doi: 10.1038/328215a0. [DOI] [PubMed] [Google Scholar]
  19. Hamill O. P., Bormann J., Sakmann B. Activation of multiple-conductance state chloride channels in spinal neurones by glycine and GABA. 1983 Oct 27-Nov 2Nature. 305(5937):805–808. doi: 10.1038/305805a0. [DOI] [PubMed] [Google Scholar]
  20. Johnson J. W., Ascher P. Glycine potentiates the NMDA response in cultured mouse brain neurons. Nature. 1987 Feb 5;325(6104):529–531. doi: 10.1038/325529a0. [DOI] [PubMed] [Google Scholar]
  21. Kaila K., Pasternack M., Saarikoski J., Voipio J. Influence of GABA-gated bicarbonate conductance on potential, current and intracellular chloride in crayfish muscle fibres. J Physiol. 1989 Sep;416:161–181. doi: 10.1113/jphysiol.1989.sp017755. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Kelly J. S., Krnjević K., Morris M. E., Yim G. K. Anionic permeability of cortical neurones. Exp Brain Res. 1969;7(1):11–31. doi: 10.1007/BF00236105. [DOI] [PubMed] [Google Scholar]
  23. Kelly J. S., Krnjević K. The action of glycine on cortical neurones. Exp Brain Res. 1969;9(2):155–163. doi: 10.1007/BF00238328. [DOI] [PubMed] [Google Scholar]
  24. Kessler M., Terramani T., Lynch G., Baudry M. A glycine site associated with N-methyl-D-aspartic acid receptors: characterization and identification of a new class of antagonists. J Neurochem. 1989 Apr;52(4):1319–1328. doi: 10.1111/j.1471-4159.1989.tb01881.x. [DOI] [PubMed] [Google Scholar]
  25. Kishimoto H., Simon J. R., Aprison M. H. Determination of the equilibrium dissociation constants and number of glycine binding sites in several areas of the rat central nervous system, using a sodium-independent system. J Neurochem. 1981 Oct;37(4):1015–1024. doi: 10.1111/j.1471-4159.1981.tb04489.x. [DOI] [PubMed] [Google Scholar]
  26. Krishtal O. A., Osipchuk YuV, Vrublevsky S. V. Properties of glycine-activated conductances in rat brain neurones. Neurosci Lett. 1988 Feb 3;84(3):271–276. doi: 10.1016/0304-3940(88)90519-8. [DOI] [PubMed] [Google Scholar]
  27. Levi G., Bernardi G., Cherubini E., Gallo V., Marciani M. G., Stanzione P. Evidence in favor of a neurotransmitter role of glycine in the rat cerebral cortex. Brain Res. 1982 Mar 18;236(1):121–131. doi: 10.1016/0006-8993(82)90039-7. [DOI] [PubMed] [Google Scholar]
  28. Misgeld U., Deisz R. A., Dodt H. U., Lux H. D. The role of chloride transport in postsynaptic inhibition of hippocampal neurons. Science. 1986 Jun 13;232(4756):1413–1415. doi: 10.1126/science.2424084. [DOI] [PubMed] [Google Scholar]
  29. Morita K., North R. A., Tokimasa T. The calcium-activated potassium conductance in guinea-pig myenteric neurones. J Physiol. 1982 Aug;329:341–354. doi: 10.1113/jphysiol.1982.sp014306. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Schwartzkroin P. A., Kunkel D. D. Electrophysiology and morphology of the developing hippocampus of fetal rabbits. J Neurosci. 1982 Apr;2(4):448–462. doi: 10.1523/JNEUROSCI.02-04-00448.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Thomas R. C. Experimental displacement of intracellular pH and the mechanism of its subsequent recovery. J Physiol. 1984 Sep;354:3P–22P. doi: 10.1113/jphysiol.1984.sp015397. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Young A. B., Snyder S. H. Strychnine binding associated with glycine receptors of the central nervous system. Proc Natl Acad Sci U S A. 1973 Oct;70(10):2832–2836. doi: 10.1073/pnas.70.10.2832. [DOI] [PMC free article] [PubMed] [Google Scholar]

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