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. 1992 Feb;105(2):470–474. doi: 10.1111/j.1476-5381.1992.tb14277.x

4-Aminopyridine and low Ca2+ differentiate presynaptic inhibition mediated by neuropeptide Y, baclofen and 2-chloroadenosine in rat hippocampal CA1 in vitro.

G J Klapstein 1, W F Colmers 1
PMCID: PMC1908646  PMID: 1313731

Abstract

1. Presynaptic inhibition is mediated by several receptors at the stratum radiatum-CA1 synapse of rat hippocampus. We tested whether the same mechanism is activated by neuropeptide Y (NPY), baclofen and 2-chloroadenosine (2-CA), reasoning that if the receptors all activated the same process, then they should all respond to indirect manipulations of transmitter release in the same manner. 2. The effects on presynaptic inhibition by the potassium channel blocker, 4-aminopyridine (4-AP) and low extracellular concentrations of Ca2+ in the presence of 4-AP were compared using evoked population excitatory postsynaptic potentials (p.e.p.s.p.) responses in the rat hippocampal slice in vitro. 3. Log concentration-effect relationships for the inhibition of excitatory transmission were constructed for all 3 drugs in normal saline, and in the presence of 30 and 100 microM 4-AP. 4-AP reduced the inhibition mediated by all three substances, 100 microM 4-AP was only slightly more effective than 30 microM. 4. Lowering extracellular Ca2+ from 1.5 to 0.75 mM in the presence of 30 microM 4-AP restored the presynaptic inhibition caused by all effective concentrations of NPY and baclofen. By contrast, inhibition caused by 2-CA was not restored by lowering Ca2+, except at concentrations of 2-CA greater than 10 microM. 5. The results are consistent with the hypothesis that presynaptic NPY Y2 and GABAB receptors both inhibit transmitter release by the inhibition of voltage-dependent Ca2+ influx, but that the A1 adenosine receptor may activate a different presynaptic mechanism.

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Selected References

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  1. Andersen P., Silfvenius H., Sundberg S. H., Sveen O., Wigström H. Functional characteristics of unmyelinated fibres in the hippocampal cortex. Brain Res. 1978 Apr 7;144(1):11–18. doi: 10.1016/0006-8993(78)90431-6. [DOI] [PubMed] [Google Scholar]
  2. Andrade R., Malenka R. C., Nicoll R. A. A G protein couples serotonin and GABAB receptors to the same channels in hippocampus. Science. 1986 Dec 5;234(4781):1261–1265. doi: 10.1126/science.2430334. [DOI] [PubMed] [Google Scholar]
  3. Ault B., Nadler J. V. Baclofen selectively inhibits transmission at synapses made by axons of CA3 pyramidal cells in the hippocampal slice. J Pharmacol Exp Ther. 1982 Nov;223(2):291–297. [PubMed] [Google Scholar]
  4. Beck S. G. 5-Carboxyamidotryptamine mimics only the 5-HT elicited hyperpolarization of hippocampal pyramidal cells via 5-HT1A receptor. Neurosci Lett. 1989 Apr 24;99(1-2):101–106. doi: 10.1016/0304-3940(89)90272-3. [DOI] [PubMed] [Google Scholar]
  5. Buckle P. J., Haas H. L. Enhancement of synaptic transmission by 4-aminopyridine in hippocampal slices of the rat. J Physiol. 1982 May;326:109–122. doi: 10.1113/jphysiol.1982.sp014180. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Colmers W. F., Klapstein G. J., Fournier A., St-Pierre S., Treherne K. A. Presynaptic inhibition by neuropeptide Y in rat hippocampal slice in vitro is mediated by a Y2 receptor. Br J Pharmacol. 1991 Jan;102(1):41–44. doi: 10.1111/j.1476-5381.1991.tb12129.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Colmers W. F., Lukowiak K., Pittman Q. J. Neuropeptide Y action in the rat hippocampal slice: site and mechanism of presynaptic inhibition. J Neurosci. 1988 Oct;8(10):3827–3837. doi: 10.1523/JNEUROSCI.08-10-03827.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Colmers W. F., Lukowiak K., Pittman Q. J. Presynaptic action of neuropeptide Y in area CA1 of the rat hippocampal slice. J Physiol. 1987 Feb;383:285–299. doi: 10.1113/jphysiol.1987.sp016409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dolphin A. C., Scott R. H. Calcium channel currents and their inhibition by (-)-baclofen in rat sensory neurones: modulation by guanine nucleotides. J Physiol. 1987 May;386:1–17. doi: 10.1113/jphysiol.1987.sp016518. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dunwiddie T. V., Fredholm B. B. Adenosine A1 receptors inhibit adenylate cyclase activity and neurotransmitter release and hyperpolarize pyramidal neurons in rat hippocampus. J Pharmacol Exp Ther. 1989 Apr;249(1):31–37. [PubMed] [Google Scholar]
  11. Egan T. M., North R. A. Acetylcholine hyperpolarizes central neurones by acting on an M2 muscarinic receptor. 1986 Jan 30-Feb 5Nature. 319(6052):405–407. doi: 10.1038/319405a0. [DOI] [PubMed] [Google Scholar]
  12. Forsythe I. D., Clements J. D. Presynaptic glutamate receptors depress excitatory monosynaptic transmission between mouse hippocampal neurones. J Physiol. 1990 Oct;429:1–16. doi: 10.1113/jphysiol.1990.sp018240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gilman A. G. G proteins: transducers of receptor-generated signals. Annu Rev Biochem. 1987;56:615–649. doi: 10.1146/annurev.bi.56.070187.003151. [DOI] [PubMed] [Google Scholar]
  14. Greene R. W., Haas H. L. Adenosine actions on CA1 pyramidal neurones in rat hippocampal slices. J Physiol. 1985 Sep;366:119–127. doi: 10.1113/jphysiol.1985.sp015788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Harrison N. L., Lovinger D. M., Lambert N. A., Teyler T. J., Prager R., Ong J., Kerr D. I. The actions of 2-hydroxy-saclofen at presynaptic GABAB receptors in the rat hippocampus. Neurosci Lett. 1990 Nov 13;119(2):272–276. doi: 10.1016/0304-3940(90)90851-y. [DOI] [PubMed] [Google Scholar]
  16. Harrison N. L. On the presynaptic action of baclofen at inhibitory synapses between cultured rat hippocampal neurones. J Physiol. 1990 Mar;422:433–446. doi: 10.1113/jphysiol.1990.sp017993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Hounsgaard J. Presynaptic inhibitory action of acetylcholine in area CA1 of the hippocampus. Exp Neurol. 1978 Dec;62(3):787–797. doi: 10.1016/0014-4886(78)90284-4. [DOI] [PubMed] [Google Scholar]
  18. Llinás R., Walton K., Bohr V. Synaptic transmission in squid giant synapse after potassium conductance blockage with external 3- and 4-aminopyridine. Biophys J. 1976 Jan;16(1):83–86. doi: 10.1016/S0006-3495(76)85664-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. MacDonald R. L., Skerritt J. H., Werz M. A. Adenosine agonists reduce voltage-dependent calcium conductance of mouse sensory neurones in cell culture. J Physiol. 1986 Jan;370:75–90. doi: 10.1113/jphysiol.1986.sp015923. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Milner J. D., North R. A., Vitek L. V. Interactions among the effects of normorphine, calcium and magnesium on transmitter release in the mouse vas deferens. Br J Pharmacol. 1982 May;76(1):45–49. doi: 10.1111/j.1476-5381.1982.tb09189.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Morrisett R. A., Mott D. D., Lewis D. V., Swartzwelder H. S., Wilson W. A. GABAB-receptor-mediated inhibition of the N-methyl-D-aspartate component of synaptic transmission in the rat hippocampus. J Neurosci. 1991 Jan;11(1):203–209. doi: 10.1523/JNEUROSCI.11-01-00203.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Newberry N. R., Nicoll R. A. A bicuculline-resistant inhibitory post-synaptic potential in rat hippocampal pyramidal cells in vitro. J Physiol. 1984 Mar;348:239–254. doi: 10.1113/jphysiol.1984.sp015107. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Scholfield C. N., Steel L. Presynaptic K-channel blockade counteracts the depressant effect of adenosine in olfactory cortex. Neuroscience. 1988 Jan;24(1):81–91. doi: 10.1016/0306-4522(88)90313-2. [DOI] [PubMed] [Google Scholar]
  24. Silinsky E. M. The biophysical pharmacology of calcium-dependent acetylcholine secretion. Pharmacol Rev. 1985 Mar;37(1):81–132. [PubMed] [Google Scholar]
  25. Walker M. W., Ewald D. A., Perney T. M., Miller R. J. Neuropeptide Y modulates neurotransmitter release and Ca2+ currents in rat sensory neurons. J Neurosci. 1988 Jul;8(7):2438–2446. doi: 10.1523/JNEUROSCI.08-07-02438.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Wanke E., Ferroni A., Malgaroli A., Ambrosini A., Pozzan T., Meldolesi J. Activation of a muscarinic receptor selectively inhibits a rapidly inactivated Ca2+ current in rat sympathetic neurons. Proc Natl Acad Sci U S A. 1987 Jun;84(12):4313–4317. doi: 10.1073/pnas.84.12.4313. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Watkins J. C., Evans R. H. Excitatory amino acid transmitters. Annu Rev Pharmacol Toxicol. 1981;21:165–204. doi: 10.1146/annurev.pa.21.040181.001121. [DOI] [PubMed] [Google Scholar]
  28. Zidichouski J. A., Chen H., Smith P. A. Neuropeptide Y activates inwardly-rectifying K(+)-channels in C-cells of amphibian sympathetic ganglia. Neurosci Lett. 1990 Sep 4;117(1-2):123–128. doi: 10.1016/0304-3940(90)90130-2. [DOI] [PubMed] [Google Scholar]
  29. Zucker R. S., Landò L. Mechanism of transmitter release: voltage hypothesis and calcium hypothesis. Science. 1986 Feb 7;231(4738):574–579. doi: 10.1126/science.2868525. [DOI] [PubMed] [Google Scholar]

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