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. 1991 Apr;435:465–481. doi: 10.1113/jphysiol.1991.sp018519

Depression of a sustained calcium current by kainate in rat hippocampal neurones in vitro.

A Nistri 1, E Cherubini 1
PMCID: PMC1181471  PMID: 1770444

Abstract

1. High-threshold, slow inactivating inward Ca2+ currents were studied in CA1 pyramidal neurones from rat hippocampal slices using the single-electrode voltage clamp technique. 2. Kainate (50-400 nM) induced a dose-dependent depression of the amplitude of the slow Ca2+ current. At a dose of 200 nM the current amplitude was reduced from -0.63 +/- -0.06 to -0.32 +/- 0.06 nA. Such an effect of kainate was associated with the development of a small inward current (-0.11 +/- 0.03 nA). Kynurenic acid (1 mM) or 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 20 microM) fully prevented these actions of kainate. 3. The structurally related kainate analogue alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA; 200 nM) depressed the slow Ca2+ current by 30 +/- 7%, an effect also blocked by CNQX. 4. In low-Na+ medium slow Ca2+ currents were followed by sustained inward tail currents. Kainate reduced both the steady-state Ca2+ current (from -0.98 +/- 0.14 to -0.63 +/- 0.15 nA) and the tail current (from -0.40 +/- 0.04 to -0.14 +/- 0.03 nA). 5. The inactivation process of the slow Ca2+ current was tested by a double-pulse protocol and was found to be enhanced by kainate. 6. Equimolar replacement of Ca2+ by Ba2+ produced larger inward currents followed by prolonged tails. Kainate reduced the Ba2+ steady-state current from -1.77 +/- 0.18 to -1.44 +/- 0.24 nA and the tail current from -0.47 +/- 0.15 to -0.17 +/- 0.05 nA. 7. In current clamp experiments Ca2+ action potentials were recorded from cells loaded with the Ca2+ chelator BAPTA. In these conditions kainate failed to reduce the Ca2+ action potential, while in the absence of BAPTA kainate shortened the Ca2+ action potentials by 30%. 8. It is suggested that low concentrations of kainate reduced the slow Ca2+ current by promoting its inactivation perhaps through a rise in free intracellular Ca2+.

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Selected References

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  1. Ben-Ari Y. Limbic seizure and brain damage produced by kainic acid: mechanisms and relevance to human temporal lobe epilepsy. Neuroscience. 1985 Feb;14(2):375–403. doi: 10.1016/0306-4522(85)90299-4. [DOI] [PubMed] [Google Scholar]
  2. Berger M. L., Tremblay E., Nitecka L., Ben-Ari Y. Maturation of kainic acid seizure-brain damage syndrome in the rat. III. Postnatal development of kainic acid binding sites in the limbic system. Neuroscience. 1984 Dec;13(4):1095–1104. doi: 10.1016/0306-4522(84)90290-2. [DOI] [PubMed] [Google Scholar]
  3. Blaxter T. J., Carlen P. L., Niesen C. Pharmacological and anatomical separation of calcium currents in rat dentate granule neurones in vitro. J Physiol. 1989 May;412:93–112. doi: 10.1113/jphysiol.1989.sp017605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. 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]
  5. Cherubini E., Rovira C., Ben-Ari Y., Nistri A. Effects of kainate on the excitability of rat hippocampal neurones. Epilepsy Res. 1990 Jan-Feb;5(1):18–27. doi: 10.1016/0920-1211(90)90062-z. [DOI] [PubMed] [Google Scholar]
  6. Constanti A., Connor J. D., Galvan M., Nistri A. Intracellularly-recorded effects of glutamate and aspartate on neurones in the guinea-pig olfactory cortex slice. Brain Res. 1980 Aug 18;195(2):403–420. doi: 10.1016/0006-8993(80)90075-x. [DOI] [PubMed] [Google Scholar]
  7. Eckert R., Chad J. E. Inactivation of Ca channels. Prog Biophys Mol Biol. 1984;44(3):215–267. doi: 10.1016/0079-6107(84)90009-9. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Gho M., King A. E., Ben-Ari Y., Cherubini E. Kainate reduces two voltage-dependent potassium conductances in rat hippocampal neurons in vitro. Brain Res. 1986 Oct 22;385(2):411–414. doi: 10.1016/0006-8993(86)91093-0. [DOI] [PubMed] [Google Scholar]
  10. Hagiwara S., Byerly L. Calcium channel. Annu Rev Neurosci. 1981;4:69–125. doi: 10.1146/annurev.ne.04.030181.000441. [DOI] [PubMed] [Google Scholar]
  11. Kay A. R., Wong R. K. Calcium current activation kinetics in isolated pyramidal neurones of the Ca1 region of the mature guinea-pig hippocampus. J Physiol. 1987 Nov;392:603–616. doi: 10.1113/jphysiol.1987.sp016799. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lester R. A., Jahr C. E. Quisqualate receptor-mediated depression of calcium currents in hippocampal neurons. Neuron. 1990 May;4(5):741–749. doi: 10.1016/0896-6273(90)90200-y. [DOI] [PubMed] [Google Scholar]
  13. London E. D., Coyle J. T. Specific binding of [3H]kainic acid to receptor sites in rat brain. Mol Pharmacol. 1979 May;15(3):492–505. [PubMed] [Google Scholar]
  14. Mayer M. L., Westbrook G. L. Mixed-agonist action of excitatory amino acids on mouse spinal cord neurones under voltage clamp. J Physiol. 1984 Sep;354:29–53. doi: 10.1113/jphysiol.1984.sp015360. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Mayer M. L., Westbrook G. L. The physiology of excitatory amino acids in the vertebrate central nervous system. Prog Neurobiol. 1987;28(3):197–276. doi: 10.1016/0301-0082(87)90011-6. [DOI] [PubMed] [Google Scholar]
  16. Meyers D. E., Barker J. L. Whole-cell patch-clamp analysis of voltage-dependent calcium conductances in cultured embryonic rat hippocampal neurons. J Neurophysiol. 1989 Mar;61(3):467–477. doi: 10.1152/jn.1989.61.3.467. [DOI] [PubMed] [Google Scholar]
  17. Monaghan D. T., Bridges R. J., Cotman C. W. The excitatory amino acid receptors: their classes, pharmacology, and distinct properties in the function of the central nervous system. Annu Rev Pharmacol Toxicol. 1989;29:365–402. doi: 10.1146/annurev.pa.29.040189.002053. [DOI] [PubMed] [Google Scholar]
  18. Murphy S. N., Miller R. J. Regulation of Ca++ influx into striatal neurons by kainic acid. J Pharmacol Exp Ther. 1989 Apr;249(1):184–193. [PubMed] [Google Scholar]
  19. Nistri A., Cherubini E. Inactivation of a slow Ca2+ current in CA1 neurones of the adult rat hippocampal slice. Neurosci Lett. 1990 Mar 26;111(1-2):102–108. doi: 10.1016/0304-3940(90)90352-a. [DOI] [PubMed] [Google Scholar]
  20. Owen D. G., Segal M., Barker J. L. A Ca-dependent Cl- conductance in cultured mouse spinal neurones. Nature. 1984 Oct 11;311(5986):567–570. doi: 10.1038/311567a0. [DOI] [PubMed] [Google Scholar]
  21. Ozawa S., Tsuzuki K., Iino M., Ogura A., Kudo Y. Three types of voltage-dependent calcium current in cultured rat hippocampal neurons. Brain Res. 1989 Aug 28;495(2):329–336. doi: 10.1016/0006-8993(89)90225-4. [DOI] [PubMed] [Google Scholar]
  22. Robinson J. H., Deadwyler S. A. Kainic acid produces depolarization of CA3 pyramidal cells in the vitro hippocampal slice. Brain Res. 1981 Sep 21;221(1):117–127. doi: 10.1016/0006-8993(81)91067-2. [DOI] [PubMed] [Google Scholar]
  23. Simon J. R., Contrera J. F., Kuhar M. J. Binding of [3H] kainic acid, and analogue of Lglutamate, to brain membranes. J Neurochem. 1976 Jan;26(1):141–147. [PubMed] [Google Scholar]
  24. Sugiyama H., Ito I., Hirono C. A new type of glutamate receptor linked to inositol phospholipid metabolism. Nature. 1987 Feb 5;325(6104):531–533. doi: 10.1038/325531a0. [DOI] [PubMed] [Google Scholar]
  25. Tillotson D. L., Gorman A. L. Localization of neuronal Ca2+ buffering near plasma membrane studied with different divalent cations. Cell Mol Neurobiol. 1983 Dec;3(4):297–310. doi: 10.1007/BF00734712. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Watkins J. C., Krogsgaard-Larsen P., Honoré T. Structure-activity relationships in the development of excitatory amino acid receptor agonists and competitive antagonists. Trends Pharmacol Sci. 1990 Jan;11(1):25–33. doi: 10.1016/0165-6147(90)90038-a. [DOI] [PubMed] [Google Scholar]
  27. Westbrook G. L., Lothman E. W. Cellular and synaptic basis of kainic acid-induced hippocampal epileptiform activity. Brain Res. 1983 Aug 22;273(1):97–109. doi: 10.1016/0006-8993(83)91098-3. [DOI] [PubMed] [Google Scholar]

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