Abstract
1. The pharmacological properties of excitatory amino acid responses on ganglion cells dissociated from the rat retina were examined with the use of the whole-cell voltage-clamp technique. 2. L-Glutamate at a concentration of 50 microM produced inward non-desensitizing currents at negative holding potentials in nearly every cell tested (83%, n = 18) In physiological solutions, L-glutamate responses reversed at approximately -9 mV, and higher concentrations of this agonist introduced a desensitizing component to the response. 3. At negative holding potentials, kainate (25-125 microM) produced inward currents in all of the cells tested (n = 37). These currents never desensitized, even at high agonist concentrations, and reversed near -6 mV. Currents induced by 50 microM-kainate were reversibly antagonized by kynurenate (100-300 microM) but not by 100 microM-2-amino-5-phosphonovalerate (APV). 4. Quisqualate generated smaller, non-desensitizing currents in only 50% of the cells tested (n = 38). Quisqualate responses reversed in polarity near -4 mV and were maximal at an agonist dose of 25 microM, with higher concentrations introducing a rapidly desensitizing component without a detectable increase in amplitude. Currents produced by quisqualate at a concentration of 50 microM were not antagonized by either 750 microM-kynurenate or 100 microM-APV. 5. N-Methyl-D-aspartate (NMDA) produced inward currents at negative holding potentials in 68% of the cells tested (n = 31), but only when magnesium was excluded from the extracellular medium. NMDA currents were non-desensitizing at agonist concentrations of up to 200 microM, with higher concentrations introducing a rapidly desensitizing component. NMDA (200 microM) responses were blocked by APV (100 microM) and kynurenate (300 microM) and reversed near -1 mV. 6. Responses generated by kainate (50-125 microM) were antagonized by quisqualate (30-250 microM). This antagonism occurred even in cells having no measurable response to quisqualate alone, suggesting the possibility that quisqualate may be acting both as an agonist, in the 50% of the cells that have the quisqualate-specific receptor, and as an antagonist, at the kainate-specific site on all cells.(ABSTRACT TRUNCATED AT 400 WORDS)
Full text
PDF
















Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Altschuler R. A., Mosinger J. L., Harmison G. G., Parakkal M. H., Wenthold R. J. Aspartate aminotransferase-like immunoreactivity as a marker for aspartate/glutamate in guinea pig photoreceptors. Nature. 1982 Aug 12;298(5875):657–659. doi: 10.1038/298657a0. [DOI] [PubMed] [Google Scholar]
- Ames A., 3rd, Pollen D. A. Neurotransmission in central nervous tissue: a study of isolated rabbit retina. J Neurophysiol. 1969 May;32(3):424–442. doi: 10.1152/jn.1969.32.3.424. [DOI] [PubMed] [Google Scholar]
- Ault B., Evans R. H., Francis A. A., Oakes D. J., Watkins J. C. Selective depression of excitatory amino acid induced depolarizations by magnesium ions in isolated spinal cord preparations. J Physiol. 1980 Oct;307:413–428. doi: 10.1113/jphysiol.1980.sp013443. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Berger S. J., McDaniel M. L., Carter J. G., Lowry O. H. Distribution of four potential transmitter amino acids in monkey retina. J Neurochem. 1977 Jan;28(1):159–163. doi: 10.1111/j.1471-4159.1977.tb07721.x. [DOI] [PubMed] [Google Scholar]
- Bloomfield S. A., Dowling J. E. Roles of aspartate and glutamate in synaptic transmission in rabbit retina. I. Outer plexiform layer. J Neurophysiol. 1985 Mar;53(3):699–713. doi: 10.1152/jn.1985.53.3.699. [DOI] [PubMed] [Google Scholar]
- Bloomfield S. A., Dowling J. E. Roles of aspartate and glutamate in synaptic transmission in rabbit retina. II. Inner plexiform layer. J Neurophysiol. 1985 Mar;53(3):714–725. doi: 10.1152/jn.1985.53.3.714. [DOI] [PubMed] [Google Scholar]
- Bolz J., Wässle H., Thier P. Pharmacological modulation of on and off ganglion cells in the cat retina. Neuroscience. 1984 Jul;12(3):875–885. doi: 10.1016/0306-4522(84)90176-3. [DOI] [PubMed] [Google Scholar]
- Crunelli V., Forda S., Kelly J. S. Blockade of amino acid-induced depolarizations and inhibition of excitatory post-synaptic potentials in rat dentate gyrus. J Physiol. 1983 Aug;341:627–640. doi: 10.1113/jphysiol.1983.sp014829. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Crunelli V., Forda S., Kelly J. S. The reversal potential of excitatory amino acid action on granule cells of the rat dentate gyrus. J Physiol. 1984 Jun;351:327–342. doi: 10.1113/jphysiol.1984.sp015248. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cull-Candy S. G., Usowicz M. M. Multiple-conductance channels activated by excitatory amino acids in cerebellar neurons. Nature. 1987 Feb 5;325(6104):525–528. doi: 10.1038/325525a0. [DOI] [PubMed] [Google Scholar]
- Davies J., Watkins J. C. Actions of D and L forms of 2-amino-5-phosphonovalerate and 2-amino-4-phosphonobutyrate in the cat spinal cord. Brain Res. 1982 Mar 11;235(2):378–386. doi: 10.1016/0006-8993(82)91017-4. [DOI] [PubMed] [Google Scholar]
- Dräger U. C., Edwards D. L., Barnstable C. J. Antibodies against filamentous components in discrete cell types of the mouse retina. J Neurosci. 1984 Aug;4(8):2025–2042. doi: 10.1523/JNEUROSCI.04-08-02025.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dräger U. C., Edwards D. L., Kleinschmidt J. Neurofilaments contain alpha-melanocyte-stimulating hormone (alpha-MSH)-like immunoreactivity. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6408–6412. doi: 10.1073/pnas.80.20.6408. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dräger U. C., Hofbauer A. Antibodies to heavy neurofilament subunit detect a subpopulation of damaged ganglion cells in retina. Nature. 1984 Jun 14;309(5969):624–626. doi: 10.1038/309624a0. [DOI] [PubMed] [Google Scholar]
- Evans R. H., Francis A. A., Jones A. W., Smith D. A., Watkins J. C. The effects of a series of omega-phosphonic alpha-carboxylic amino acids on electrically evoked and excitant amino acid-induced responses in isolated spinal cord preparations. Br J Pharmacol. 1982 Jan;75(1):65–75. doi: 10.1111/j.1476-5381.1982.tb08758.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fenwick E. M., Marty A., Neher E. A patch-clamp study of bovine chromaffin cells and of their sensitivity to acetylcholine. J Physiol. 1982 Oct;331:577–597. doi: 10.1113/jphysiol.1982.sp014393. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fonnum F. Glutamate: a neurotransmitter in mammalian brain. J Neurochem. 1984 Jan;42(1):1–11. doi: 10.1111/j.1471-4159.1984.tb09689.x. [DOI] [PubMed] [Google Scholar]
- Fukuda Y. A three-group classification of rat retinal ganglion cells: histological and physiological studies. Brain Res. 1977 Jan 7;119(2):327–334. doi: 10.1016/0006-8993(77)90314-6. [DOI] [PubMed] [Google Scholar]
- Ganong A. H., Jones A. W., Watkins J. C., Cotman C. W. Parallel antagonism of synaptic transmission and kainate/quisqualate responses in the hippocampus by piperazine-2,3-dicarboxylic acid analogs. J Neurosci. 1986 Apr;6(4):930–937. doi: 10.1523/JNEUROSCI.06-04-00930.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ganong A. H., Lanthorn T. H., Cotman C. W. Kynurenic acid inhibits synaptic and acidic amino acid-induced responses in the rat hippocampus and spinal cord. Brain Res. 1983 Aug 22;273(1):170–174. doi: 10.1016/0006-8993(83)91108-3. [DOI] [PubMed] [Google Scholar]
- Hablitz J. J., Langmoen I. A. N-methyl-D-aspartate receptor antagonists reduce synaptic excitation in the hippocampus. J Neurosci. 1986 Jan;6(1):102–106. doi: 10.1523/JNEUROSCI.06-01-00102.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hamill O. P., Marty A., Neher E., Sakmann B., Sigworth F. J. Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches. Pflugers Arch. 1981 Aug;391(2):85–100. doi: 10.1007/BF00656997. [DOI] [PubMed] [Google Scholar]
- Huettner J. E., Baughman R. W. Primary culture of identified neurons from the visual cortex of postnatal rats. J Neurosci. 1986 Oct;6(10):3044–3060. doi: 10.1523/JNEUROSCI.06-10-03044.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ikeda H., Sheardown M. J. Aspartate may be an excitatory transmitter mediating visual excitation of "sustained" but not "transient" cells in the cat retina: iontophoretic studies in vivo. Neuroscience. 1982 Jan;7(1):25–36. doi: 10.1016/0306-4522(82)90150-6. [DOI] [PubMed] [Google Scholar]
- Ishida A. T., Neyton J. Quisqualate and L-glutamate inhibit retinal horizontal-cell responses to kainate. Proc Natl Acad Sci U S A. 1985 Mar;82(6):1837–1841. doi: 10.1073/pnas.82.6.1837. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jahr C. E., Jessell T. M. Synaptic transmission between dorsal root ganglion and dorsal horn neurons in culture: antagonism of monosynaptic excitatory postsynaptic potentials and glutamate excitation by kynurenate. J Neurosci. 1985 Aug;5(8):2281–2289. doi: 10.1523/JNEUROSCI.05-08-02281.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jahr C. E., Stevens C. F. Glutamate activates multiple single channel conductances in hippocampal neurons. Nature. 1987 Feb 5;325(6104):522–525. doi: 10.1038/325522a0. [DOI] [PubMed] [Google Scholar]
- Johnson J. L. Glutamic acid as a synaptic transmitter in the nervous system. A review. Brain Res. 1972 Feb 11;37(1):1–19. doi: 10.1016/0006-8993(72)90343-5. [DOI] [PubMed] [Google Scholar]
- Leifer D., Lipton S. A., Barnstable C. J., Masland R. H. Monoclonal antibody to Thy-1 enhances regeneration of processes by rat retinal ganglion cells in culture. Science. 1984 Apr 20;224(4646):303–306. doi: 10.1126/science.6143400. [DOI] [PubMed] [Google Scholar]
- Lipton S. A., Tauck D. L. Voltage-dependent conductances of solitary ganglion cells dissociated from the rat retina. J Physiol. 1987 Apr;385:361–391. doi: 10.1113/jphysiol.1987.sp016497. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lukasiewicz P. D., McReynolds J. S. Synaptic transmission at N-methyl-D-aspartate receptors in the proximal retina of the mudpuppy. J Physiol. 1985 Oct;367:99–115. doi: 10.1113/jphysiol.1985.sp015816. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mayer M. L., Westbrook G. L. The action of N-methyl-D-aspartic acid on mouse spinal neurones in culture. J Physiol. 1985 Apr;361:65–90. doi: 10.1113/jphysiol.1985.sp015633. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Nowak L., Bregestovski P., Ascher P., Herbet A., Prochiantz A. Magnesium gates glutamate-activated channels in mouse central neurones. Nature. 1984 Feb 2;307(5950):462–465. doi: 10.1038/307462a0. [DOI] [PubMed] [Google Scholar]
- O'Brien R. J., Fischbach G. D. Characterization of excitatory amino acid receptors expressed by embryonic chick motoneurons in vitro. J Neurosci. 1986 Nov;6(11):3275–3283. doi: 10.1523/JNEUROSCI.06-11-03275.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Perkins M. N., Stone T. W. An iontophoretic investigation of the actions of convulsant kynurenines and their interaction with the endogenous excitant quinolinic acid. Brain Res. 1982 Sep 9;247(1):184–187. doi: 10.1016/0006-8993(82)91048-4. [DOI] [PubMed] [Google Scholar]
- Perry V. H. The ganglion cell layer of the retina of the rat: a Golgi study. Proc R Soc Lond B Biol Sci. 1979 May 23;204(1156):363–375. doi: 10.1098/rspb.1979.0033. [DOI] [PubMed] [Google Scholar]
- Slaughter M. M., Miller R. F. The role of excitatory amino acid transmitters in the mudpuppy retina: an analysis with kainic acid and N-methyl aspartate. J Neurosci. 1983 Aug;3(8):1701–1711. doi: 10.1523/JNEUROSCI.03-08-01701.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Thomson A. M., West D. C., Lodge D. An N-methylaspartate receptor-mediated synapse in rat cerebral cortex: a site of action of ketamine? Nature. 1985 Feb 7;313(6002):479–481. doi: 10.1038/313479a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Westbrook G. L., Mayer M. L. Glutamate currents in mammalian spinal neurons: resolution of a paradox. Brain Res. 1984 Jun 3;301(2):375–379. doi: 10.1016/0006-8993(84)91107-7. [DOI] [PubMed] [Google Scholar]