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. 1992 Aug 1;89(15):6881–6885. doi: 10.1073/pnas.89.15.6881

Increasing binding affinity of agonists to glutamate receptors increases synaptic responses at glutamatergic synapses.

K Shahi 1, M Baudry 1
PMCID: PMC49608  PMID: 1379724

Abstract

This study examined the relationship between the affinity of glutamate agonists for the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors and the characteristics of the physiological responses elicited by endogenous activation of the AMPA receptors. We tested the effects of chaotropic ions on [3H]AMPA binding in synaptic membranes as well as on synaptic responses elicited in CA1 by electrical stimulation of the Schaffer/commissural pathway in the in vitro hippocampal slice preparation. Of the chaotropic ions tested, only perchlorate and thiocyanate produced large increases in [3H]AMPA binding to synaptic membranes. The effect was due to an increase in affinity for agonists, as shown by a shift of the displacement curves of 6-cyano-7-nitro[3H]-quinoxaline-2,3-dione binding by AMPA or glutamate. The effect of thiocyanate on [3H]AMPA binding was extremely sensitive to temperature, as the binding was increased almost 10-fold at 0 degree C but only 2- to 3-fold at 35 degrees C. The effect of perchlorate was only weakly temperature dependent. Similarly, thiocyanate and perchlorate were the only chaotropic ions tested that increased the initial slope and amplitude of the extracellularly recorded potentials evoked in CA1 dendritic field. Both ions did not change paired-pulse facilitation, an index of transmitter release, or fiber volley amplitude, an index of afferent recruitment. The chaotropic ions had no significant effects on either [3H]glutamate binding to the N-methyl-D-aspartate receptor or N-methyl-D-aspartate receptor-mediated synaptic responses. Finally, the effect of perchlorate on synaptic responses was significantly reduced after induction of long-term potentiation. These results indicate that an increase in affinity of the AMPA receptors for their agonists results in increased synaptic responses and strongly suggest that characteristics of the AMPA receptor are modified following long-term potentiation.

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Selected References

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  1. Baudry M., Massicotte G., Hauge S. Phosphatidylserine increases the affinity of the AMPA/quisqualate receptor in rat brain membranes. Behav Neural Biol. 1991 Mar;55(2):137–140. doi: 10.1016/0163-1047(91)80134-z. [DOI] [PubMed] [Google Scholar]
  2. Baudry M., Monaghan D., Cotman C., Altar C. A. Regional distribution of alpha-[3H]amino-3-hydroxy-5-methylisoxazole-4-propionic acid binding sites in rat brain: effect of chemical modification of SH- groups in tissue sections. J Neurochem. 1990 May;54(5):1682–1688. doi: 10.1111/j.1471-4159.1990.tb01222.x. [DOI] [PubMed] [Google Scholar]
  3. Bliss T. V., Lomo T. Long-lasting potentiation of synaptic transmission in the dentate area of the anaesthetized rabbit following stimulation of the perforant path. J Physiol. 1973 Jul;232(2):331–356. doi: 10.1113/jphysiol.1973.sp010273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Honoré T., Drejer J. Chaotropic ions affect the conformation of quisqualate receptors in rat cortical membranes. J Neurochem. 1988 Aug;51(2):457–461. doi: 10.1111/j.1471-4159.1988.tb01060.x. [DOI] [PubMed] [Google Scholar]
  5. Hunter C., Wheaton K. D., Wenthold R. J. Solubilization and partial purification of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid binding sites from rat brain. J Neurochem. 1990 Jan;54(1):118–125. doi: 10.1111/j.1471-4159.1990.tb13290.x. [DOI] [PubMed] [Google Scholar]
  6. Kauer J. A., Malenka R. C., Nicoll R. A. A persistent postsynaptic modification mediates long-term potentiation in the hippocampus. Neuron. 1988 Dec;1(10):911–917. doi: 10.1016/0896-6273(88)90148-1. [DOI] [PubMed] [Google Scholar]
  7. Kessler M., Petersen G., Vu H. M., Baudry M., Lynch G. L-phenylalanyl-L-glutamate-stimulated, chloride-dependent glutamate binding represents glutamate sequestration mediated by an exchange system. J Neurochem. 1987 Apr;48(4):1191–1200. doi: 10.1111/j.1471-4159.1987.tb05646.x. [DOI] [PubMed] [Google Scholar]
  8. Larson J., Wong D., Lynch G. Patterned stimulation at the theta frequency is optimal for the induction of hippocampal long-term potentiation. Brain Res. 1986 Mar 19;368(2):347–350. doi: 10.1016/0006-8993(86)90579-2. [DOI] [PubMed] [Google Scholar]
  9. Lynch G., Baudry M. Reevaluating the constraints on hypotheses regarding LTP expression. Hippocampus. 1991 Jan;1(1):9–14. doi: 10.1002/hipo.450010103. [DOI] [PubMed] [Google Scholar]
  10. Magleby K. L., Stevens C. F. A quantitative description of end-plate currents. J Physiol. 1972 May;223(1):173–197. doi: 10.1113/jphysiol.1972.sp009840. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Massicotte G., Baudry M. Modulation of DL-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)/quisqualate receptors by phospholipase A2 treatment. Neurosci Lett. 1990 Oct 16;118(2):245–248. doi: 10.1016/0304-3940(90)90638-p. [DOI] [PubMed] [Google Scholar]
  12. Massicotte G., Baudry M. Triggers and substrates of hippocampal synaptic plasticity. Neurosci Biobehav Rev. 1991 Fall;15(3):415–423. doi: 10.1016/s0149-7634(05)80034-x. [DOI] [PubMed] [Google Scholar]
  13. Massicotte G., Kessler M., Lynch G., Baudry M. N-Methyl-D-aspartate and quisqualate/DL-alpha-amino-3-hydroxy-5- methylisoxazole-4-propionic acid receptors: differential regulation by phospholipase C treatment. Mol Pharmacol. 1990 Feb;37(2):278–285. [PubMed] [Google Scholar]
  14. Massicotte G., Oliver M. W., Lynch G., Baudry M. Effect of bromophenacyl bromide, a phospholipase A2 inhibitor, on the induction and maintenance of LTP in hippocampal slices. Brain Res. 1990 Dec 24;537(1-2):49–53. doi: 10.1016/0006-8993(90)90338-c. [DOI] [PubMed] [Google Scholar]
  15. Monaghan D. T., Olverman H. J., Nguyen L., Watkins J. C., Cotman C. W. Two classes of N-methyl-D-aspartate recognition sites: differential distribution and differential regulation by glycine. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9836–9840. doi: 10.1073/pnas.85.24.9836. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Muller D., Joly M., Lynch G. Contributions of quisqualate and NMDA receptors to the induction and expression of LTP. Science. 1988 Dec 23;242(4886):1694–1697. doi: 10.1126/science.2904701. [DOI] [PubMed] [Google Scholar]
  17. Muller D., Lynch G. Long-term potentiation differentially affects two components of synaptic responses in hippocampus. Proc Natl Acad Sci U S A. 1988 Dec;85(23):9346–9350. doi: 10.1073/pnas.85.23.9346. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Möhler H., Okada T. Properties of gamma-aminobutyric acid receptor binding with (+)-[3H]bicuculline methiodide in rat cerebellum. Mol Pharmacol. 1978 Mar;14(2):256–265. [PubMed] [Google Scholar]
  19. Nelson P. G., Pun R. Y., Westbrook G. L. Synaptic excitation in cultures of mouse spinal cord neurones: receptor pharmacology and behaviour of synaptic currents. J Physiol. 1986 Mar;372:169–190. doi: 10.1113/jphysiol.1986.sp016003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Olsen R. W., Szamraj O., Houser C. R. [3H]AMPA binding to glutamate receptor subpopulations in rat brain. Brain Res. 1987 Feb 3;402(2):243–254. doi: 10.1016/0006-8993(87)90030-8. [DOI] [PubMed] [Google Scholar]
  21. Tang C. M., Dichter M., Morad M. Quisqualate activates a rapidly inactivating high conductance ionic channel in hippocampal neurons. Science. 1989 Mar 17;243(4897):1474–1477. doi: 10.1126/science.2467378. [DOI] [PubMed] [Google Scholar]
  22. Terramani T., Kessler M., Lynch G., Baudry M. Effects of thiol-reagents on [3H]alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid binding to rat telencephalic membranes. Mol Pharmacol. 1988 Aug;34(2):117–123. [PubMed] [Google Scholar]
  23. Thio L. L., Clifford D. B., Zorumski C. F. Characterization of quisqualate receptor desensitization in cultured postnatal rat hippocampal neurons. J Neurosci. 1991 Nov;11(11):3430–3441. doi: 10.1523/JNEUROSCI.11-11-03430.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Tocco G., Devgan K. K., Hauge S. A., Weiss C., Baudry M., Thompson R. F. Classical conditioning selectively increases AMPA receptor binding in rabbit hippocampus. Brain Res. 1991 Sep 20;559(2):331–336. doi: 10.1016/0006-8993(91)90020-v. [DOI] [PubMed] [Google Scholar]
  25. Tocco G., Maren S., Shors T. J., Baudry M., Thompson R. F. Long-term potentiation is associated with increased [3H]AMPA binding in rat hippocampus. Brain Res. 1992 Feb 28;573(2):228–234. doi: 10.1016/0006-8993(92)90767-4. [DOI] [PubMed] [Google Scholar]
  26. Xiao P., Staubli U., Kessler M., Lynch G. Selective effects of aniracetam across receptor types and forms of synaptic facilitation in hippocampus. Hippocampus. 1991 Oct;1(4):373–380. doi: 10.1002/hipo.450010405. [DOI] [PubMed] [Google Scholar]

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