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. 1989 Oct;417:567–578. doi: 10.1113/jphysiol.1989.sp017819

Characterization of inhibition mediated by adenosine in the hippocampus of the rat in vitro.

U Gerber 1, R W Greene 1, H L Haas 1, D R Stevens 1
PMCID: PMC1189284  PMID: 2559967

Abstract

1. Intracellular recordings with single-electrode voltage clamp were employed to study the mechanism of adenosine-elicited inhibition of CA1 neurones of the rat in vitro. 2. Adenosine elicits a steady-state outward current in association with an increase in conductance. The driving force varied with external potassium concentration as predicted by the Nernst equation for a change primarily in potassium permeability. 3. Adenosine current was blocked by high concentrations of 4-aminopyridine or barium. In the majority of neurones this current was voltage insensitive. In the remainder, the current was inwardly rectifying. The rectification was blocked by tetraethylammonium. 4. When the adenosine-elicited potassium current was blocked, slow inward currents, normally carried by calcium, were unaffected by adenosine. We conclude that this adenosine inhibition is mediated by an increase in a voltage- and calcium-insensitive potassium conductance in CA1 neurones.

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Selected References

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  1. Alger B. E., Nicoll R. A. Epileptiform burst afterhyperolarization: calcium-dependent potassium potential in hippocampal CA1 pyramidal cells. Science. 1980 Dec 5;210(4474):1122–1124. doi: 10.1126/science.7444438. [DOI] [PubMed] [Google Scholar]
  2. Andrade R., Nicoll R. A. Pharmacologically distinct actions of serotonin on single pyramidal neurones of the rat hippocampus recorded in vitro. J Physiol. 1987 Dec;394:99–124. doi: 10.1113/jphysiol.1987.sp016862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Brezina V., Eckert R., Erxleben C. Modulation of potassium conductances by an endogenous neuropeptide in neurones of Aplysia californica. J Physiol. 1987 Jan;382:267–290. doi: 10.1113/jphysiol.1987.sp016367. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brezina V. Guanosine 5'-triphosphate analogue activates potassium current modulated by neurotransmitters in Aplysia neurones. J Physiol. 1988 Dec;407:15–40. doi: 10.1113/jphysiol.1988.sp017401. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Brown D. A., Griffith W. H. Persistent slow inward calcium current in voltage-clamped hippocampal neurones of the guinea-pig. J Physiol. 1983 Apr;337:303–320. doi: 10.1113/jphysiol.1983.sp014625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Colino A., Halliwell J. V. Differential modulation of three separate K-conductances in hippocampal CA1 neurons by serotonin. Nature. 1987 Jul 2;328(6125):73–77. doi: 10.1038/328073a0. [DOI] [PubMed] [Google Scholar]
  7. Connor J. A. Calcium current in molluscan neurones: measurement under conditions which maximize its visibility. J Physiol. 1979 Jan;286:41–60. doi: 10.1113/jphysiol.1979.sp012606. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dolphin A. C., Forda S. R., Scott R. H. Calcium-dependent currents in cultured rat dorsal root ganglion neurones are inhibited by an adenosine analogue. J Physiol. 1986 Apr;373:47–61. doi: 10.1113/jphysiol.1986.sp016034. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dunwiddie T. V., Haas H. L. Adenosine increases synaptic facilitation in the in vitro rat hippocampus: evidence for a presynaptic site of action. J Physiol. 1985 Dec;369:365–377. doi: 10.1113/jphysiol.1985.sp015907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Dunwiddie T. V., Hoffer B. J. Adenine nucleotides and synaptic transmission in the in vitro rat hippocampus. Br J Pharmacol. 1980 May;69(1):59–68. doi: 10.1111/j.1476-5381.1980.tb10883.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fox A. P., Nowycky M. C., Tsien R. W. Kinetic and pharmacological properties distinguishing three types of calcium currents in chick sensory neurones. J Physiol. 1987 Dec;394:149–172. doi: 10.1113/jphysiol.1987.sp016864. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. Greene R. W., Haas H. L., Hermann A. Effects of caffeine on hippocampal pyramidal cells in vitro. Br J Pharmacol. 1985 May;85(1):163–169. doi: 10.1111/j.1476-5381.1985.tb08843.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Gähwiler B. H., Brown D. A. GABAB-receptor-activated K+ current in voltage-clamped CA3 pyramidal cells in hippocampal cultures. Proc Natl Acad Sci U S A. 1985 Mar;82(5):1558–1562. doi: 10.1073/pnas.82.5.1558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Haas H. L., Greene R. W. Adenosine enhances afterhyperpolarization and accommodation in hippocampal pyramidal cells. Pflugers Arch. 1984 Nov;402(3):244–247. doi: 10.1007/BF00585506. [DOI] [PubMed] [Google Scholar]
  16. Haas H. L., Greene R. W. Endogenous adenosine inhibits hippocampal CA1 neurones: further evidence from extra- and intracellular recording. Naunyn Schmiedebergs Arch Pharmacol. 1988 May;337(5):561–565. doi: 10.1007/BF00182732. [DOI] [PubMed] [Google Scholar]
  17. Halliwell J. V., Adams P. R. Voltage-clamp analysis of muscarinic excitation in hippocampal neurons. Brain Res. 1982 Oct 28;250(1):71–92. doi: 10.1016/0006-8993(82)90954-4. [DOI] [PubMed] [Google Scholar]
  18. Halliwell J. V., Scholfield C. N. Somatically recorded Ca-currents in guinea-pig hippocampal and olfactory cortex neurones are resistant to adenosine action. Neurosci Lett. 1984 Sep 7;50(1-3):13–18. doi: 10.1016/0304-3940(84)90454-3. [DOI] [PubMed] [Google Scholar]
  19. Johnston D., Hablitz J. J., Wilson W. A. Voltage clamp discloses slow inward current in hippocampal burst-firing neurones. Nature. 1980 Jul 24;286(5771):391–393. doi: 10.1038/286391a0. [DOI] [PubMed] [Google Scholar]
  20. Lee K. S., Reddington M., Schubert P., Kreutzberg G. Regulation of the strength of adenosine modulation in the hippocampus by a differential distribution of the density of A1 receptors. Brain Res. 1983 Jan 31;260(1):156–159. doi: 10.1016/0006-8993(83)90779-5. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. North R. A., Williams J. T., Surprenant A., Christie M. J. Mu and delta receptors belong to a family of receptors that are coupled to potassium channels. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5487–5491. doi: 10.1073/pnas.84.15.5487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Okada Y., Ozawa S. Inhibitory action of adenosine on synaptic transmission in the hippocampus of the guinea pig in vitro. Eur J Pharmacol. 1980 Dec 19;68(4):483–492. doi: 10.1016/0014-2999(80)90424-0. [DOI] [PubMed] [Google Scholar]
  24. Phillis J. W., Kostopoulos G. K., Limacher J. J. A potent depressant action of adenine derivatives on cerebral cortical neurones. Eur J Pharmacol. 1975 Jan;30(1):125–129. doi: 10.1016/0014-2999(75)90214-9. [DOI] [PubMed] [Google Scholar]
  25. Pollock J. D., Bernier L., Camardo J. S. Serotonin and cyclic adenosine 3':5'-monophosphate modulate the potassium current in tail sensory neurons in the pleural ganglion of Aplysia. J Neurosci. 1985 Jul;5(7):1862–1871. doi: 10.1523/JNEUROSCI.05-07-01862.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Proctor W. R., Dunwiddie T. V. Adenosine inhibits calcium spikes in hippocampal pyramidal neurons in vitro. Neurosci Lett. 1983 Feb 21;35(2):197–201. doi: 10.1016/0304-3940(83)90550-5. [DOI] [PubMed] [Google Scholar]
  27. Pull I., McIlwain H. Adenine derivatives as neurohumoral agents in the brain. The quantities liberated on excitation of superfused cerebral tissues. Biochem J. 1972 Dec;130(4):975–981. doi: 10.1042/bj1300975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Schwartzkroin P. A., Slawsky M. Probable calcium spikes in hippocampal neurons. Brain Res. 1977 Oct 21;135(1):157–161. doi: 10.1016/0006-8993(77)91060-5. [DOI] [PubMed] [Google Scholar]
  29. Segal M. Intracellular analysis of a postsynaptic action of adenosine in the rat hippocampus. Eur J Pharmacol. 1982 Apr 23;79(3-4):193–199. doi: 10.1016/0014-2999(82)90625-2. [DOI] [PubMed] [Google Scholar]
  30. Shuster M. J., Siegelbaum S. A. Pharmacological characterization of the serotonin-sensitive potassium channel of Aplysia sensory neurons. J Gen Physiol. 1987 Oct;90(4):587–608. doi: 10.1085/jgp.90.4.587. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Siegelbaum S. A., Camardo J. S., Kandel E. R. Serotonin and cyclic AMP close single K+ channels in Aplysia sensory neurones. Nature. 1982 Sep 30;299(5882):413–417. doi: 10.1038/299413a0. [DOI] [PubMed] [Google Scholar]
  32. Stanfield P. R. Tetraethylammonium ions and the potassium permeability of excitable cells. Rev Physiol Biochem Pharmacol. 1983;97:1–67. doi: 10.1007/BFb0035345. [DOI] [PubMed] [Google Scholar]
  33. Thompson S. H. Three pharmacologically distinct potassium channels in molluscan neurones. J Physiol. 1977 Feb;265(2):465–488. doi: 10.1113/jphysiol.1977.sp011725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Trussell L. O., Jackson M. B. Adenosine-activated potassium conductance in cultured striatal neurons. Proc Natl Acad Sci U S A. 1985 Jul;82(14):4857–4861. doi: 10.1073/pnas.82.14.4857. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Trussell L. O., Jackson M. B. Dependence of an adenosine-activated potassium current on a GTP-binding protein in mammalian central neurons. J Neurosci. 1987 Oct;7(10):3306–3316. doi: 10.1523/JNEUROSCI.07-10-03306.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Vizi E. S., Knoll J. The inhibitory effect of adenosine and related nucleotides on the release of acetylcholine. Neuroscience. 1976;1(5):391–398. doi: 10.1016/0306-4522(76)90132-9. [DOI] [PubMed] [Google Scholar]
  37. Williams J. T., Colmers W. F., Pan Z. Z. Voltage- and ligand-activated inwardly rectifying currents in dorsal raphe neurons in vitro. J Neurosci. 1988 Sep;8(9):3499–3506. doi: 10.1523/JNEUROSCI.08-09-03499.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Williams J. T., Henderson G., North R. A. Characterization of alpha 2-adrenoceptors which increase potassium conductance in rat locus coeruleus neurones. Neuroscience. 1985 Jan;14(1):95–101. doi: 10.1016/0306-4522(85)90166-6. [DOI] [PubMed] [Google Scholar]
  39. Williams J. T., North R. A., Tokimasa T. Inward rectification of resting and opiate-activated potassium currents in rat locus coeruleus neurons. J Neurosci. 1988 Nov;8(11):4299–4306. doi: 10.1523/JNEUROSCI.08-11-04299.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Yakel J. L., Trussell L. O., Jackson M. B. Three serotonin responses in cultured mouse hippocampal and striatal neurons. J Neurosci. 1988 Apr;8(4):1273–1285. doi: 10.1523/JNEUROSCI.08-04-01273.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Zetterström T., Vernet L., Ungerstedt U., Tossman U., Jonzon B., Fredholm B. B. Purine levels in the intact rat brain. Studies with an implanted perfused hollow fibre. Neurosci Lett. 1982 Apr 16;29(2):111–115. doi: 10.1016/0304-3940(82)90338-x. [DOI] [PubMed] [Google Scholar]

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