Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Dec 1;88(23):10759–10763. doi: 10.1073/pnas.88.23.10759

(-)-baclofen and gamma-aminobutyric acid inhibit calcium currents in isolated retinal ganglion cells.

V P Bindokas 1, A T Ishida 1
PMCID: PMC53010  PMID: 1660149

Abstract

Of the various synaptic inputs known to converge upon retinal ganglion cells, the major inhibitory inputs are thought to be GABAergic. Although gamma-aminobutyric acid (GABA) is known to activate anion-selective ion channels in retinal ganglion cells, we have tested the possibility that GABA can also modulate cationic conductances in these cells, as seen in other central and peripheral neurons. Specifically, we have made whole-cell patch-clamp recordings to test whether voltage-gated calcium currents in isolated goldfish retinal ganglion cells are sensitive to GABAB receptor ligands. (-)-Baclofen and GABA inhibited calcium currents activated by moderately long depolarizations and, during large depolarizations (e.g., to 0 mV), also appeared to accelerate the rate of current decay. The calcium current inhibition induced by (-)-baclofen and GABA was not prevented by 2-hydroxysaclofen, phaclofen, or bicuculline, even though bicuculline suppressed a GABA-activated conductance in these cells. These results demonstrate the presence of baclofen- and GABA-sensitive calcium currents in vertebrate retinal ganglion cells as well as the coexistence of GABAA and GABAB receptors in individual retinal ganglion cells.

Full text

PDF
10759

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Ahlijanian M. K., Westenbroek R. E., Catterall W. A. Subunit structure and localization of dihydropyridine-sensitive calcium channels in mammalian brain, spinal cord, and retina. Neuron. 1990 Jun;4(6):819–832. doi: 10.1016/0896-6273(90)90135-3. [DOI] [PubMed] [Google Scholar]
  2. Barnes S., Hille B. Ionic channels of the inner segment of tiger salamander cone photoreceptors. J Gen Physiol. 1989 Oct;94(4):719–743. doi: 10.1085/jgp.94.4.719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bean B. P. Neurotransmitter inhibition of neuronal calcium currents by changes in channel voltage dependence. Nature. 1989 Jul 13;340(6229):153–156. doi: 10.1038/340153a0. [DOI] [PubMed] [Google Scholar]
  4. Bormann J. Electrophysiology of GABAA and GABAB receptor subtypes. Trends Neurosci. 1988 Mar;11(3):112–116. doi: 10.1016/0166-2236(88)90156-7. [DOI] [PubMed] [Google Scholar]
  5. Byerly L., Moody W. J. Intracellular calcium ions and calcium currents in perfused neurones of the snail, Lymnaea stagnalis. J Physiol. 1984 Jul;352:637–652. doi: 10.1113/jphysiol.1984.sp015314. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chun M. H., Wässle H. GABA-like immunoreactivity in the cat retina: electron microscopy. J Comp Neurol. 1989 Jan 1;279(1):55–67. doi: 10.1002/cne.902790106. [DOI] [PubMed] [Google Scholar]
  7. Cohen B. N., Fain G. L., Fain M. J. GABA and glycine channels in isolated ganglion cells from the goldfish retina. J Physiol. 1989 Nov;418:53–82. doi: 10.1113/jphysiol.1989.sp017828. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dacheux R. F., Frumkes T. E., Miller R. F. Pathways and polarities of synaptic interactions in the inner retina of the mudpuppy: I. Synaptic blocking studies. Brain Res. 1979 Jan 26;161(1):1–12. doi: 10.1016/0006-8993(79)90191-4. [DOI] [PubMed] [Google Scholar]
  9. Deisz R. A., Lux H. D. gamma-Aminobutyric acid-induced depression of calcium currents of chick sensory neurons. Neurosci Lett. 1985 May 14;56(2):205–210. doi: 10.1016/0304-3940(85)90130-2. [DOI] [PubMed] [Google Scholar]
  10. Désarmenien M., Feltz P., Occhipinti G., Santangelo F., Schlichter R. Coexistence of GABAA and GABAB receptors on A delta and C primary afferents. Br J Pharmacol. 1984 Feb;81(2):327–333. doi: 10.1111/j.1476-5381.1984.tb10082.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Feltz A., Demeneix B., Feltz P., Taleb O., Trouslard J., Bossu J. L., Dupont J. L. Intracellular effectors and modulators of GABA-A and GABA-B receptors: a commentary. Biochimie. 1987 Apr;69(4):395–406. doi: 10.1016/0300-9084(87)90031-9. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. 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]
  15. Horn R., Marty A. Muscarinic activation of ionic currents measured by a new whole-cell recording method. J Gen Physiol. 1988 Aug;92(2):145–159. doi: 10.1085/jgp.92.2.145. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Inoue M., Oomura Y., Yakushiji T., Akaike N. Intracellular calcium ions decrease the affinity of the GABA receptor. Nature. 1986 Nov 13;324(6093):156–158. doi: 10.1038/324156a0. [DOI] [PubMed] [Google Scholar]
  17. Ishida A. T., Bindokas V. P., Nuccitelli R. Calcium ion levels in resting and depolarized goldfish retinal ganglion cell somata and growth cones. J Neurophysiol. 1991 Apr;65(4):968–979. doi: 10.1152/jn.1991.65.4.968. [DOI] [PubMed] [Google Scholar]
  18. Ishida A. T., Cheng M. H. Cold inhibits neurite outgrowth from single retinal ganglion cells isolated from adult goldfish. Exp Eye Res. 1991 Feb;52(2):175–191. doi: 10.1016/0014-4835(91)90257-f. [DOI] [PubMed] [Google Scholar]
  19. Ishida A. T., Cohen B. N. GABA-activated whole-cell currents in isolated retinal ganglion cells. J Neurophysiol. 1988 Aug;60(2):381–396. doi: 10.1152/jn.1988.60.2.381. [DOI] [PubMed] [Google Scholar]
  20. Ishida A. T. Regenerative sodium and calcium currents in goldfish retinal ganglion cell somata. Vision Res. 1991;31(3):477–485. doi: 10.1016/0042-6989(91)90099-q. [DOI] [PubMed] [Google Scholar]
  21. Kaneko A., Tachibana M. Effects of gamma-aminobutyric acid on isolated cone photoreceptors of the turtle retina. J Physiol. 1986 Apr;373:443–461. doi: 10.1113/jphysiol.1986.sp016057. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Karschin A., Lipton S. A. Calcium channels in solitary retinal ganglion cells from post-natal rat. J Physiol. 1989 Nov;418:379–396. doi: 10.1113/jphysiol.1989.sp017847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kerr D. I., Ong J., Johnston G. A., Abbenante J., Prager R. H. 2-Hydroxy-saclofen: an improved antagonist at central and peripheral GABAB receptors. Neurosci Lett. 1988 Sep 23;92(1):92–96. doi: 10.1016/0304-3940(88)90748-3. [DOI] [PubMed] [Google Scholar]
  24. Llano I., Leresche N., Marty A. Calcium entry increases the sensitivity of cerebellar Purkinje cells to applied GABA and decreases inhibitory synaptic currents. Neuron. 1991 Apr;6(4):565–574. doi: 10.1016/0896-6273(91)90059-9. [DOI] [PubMed] [Google Scholar]
  25. Maguire G., Maple B., Lukasiewicz P., Werblin F. Gamma-aminobutyrate type B receptor modulation of L-type calcium channel current at bipolar cell terminals in the retina of the tiger salamander. Proc Natl Acad Sci U S A. 1989 Dec;86(24):10144–10147. doi: 10.1073/pnas.86.24.10144. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Maruyama T., Behrends J. C., Akaike N. Inhibition of the voltage-dependent calcium currents in isolated frog sensory neurons by GABA-related agonistic compounds. Neurosci Res. 1988 Dec;6(2):97–105. doi: 10.1016/0168-0102(88)90011-9. [DOI] [PubMed] [Google Scholar]
  27. Nicoll R. A. The coupling of neurotransmitter receptors to ion channels in the brain. Science. 1988 Jul 29;241(4865):545–551. doi: 10.1126/science.2456612. [DOI] [PubMed] [Google Scholar]
  28. Scott R. H., Dolphin A. C. Regulation of calcium currents by a GTP analogue: potentiation of (-)-baclofen-mediated inhibition. Neurosci Lett. 1986 Aug 15;69(1):59–64. doi: 10.1016/0304-3940(86)90414-3. [DOI] [PubMed] [Google Scholar]
  29. Slaughter M. M., Bai S. H. Differential effects of baclofen on sustained and transient cells in the mudpuppy retina. J Neurophysiol. 1989 Feb;61(2):374–381. doi: 10.1152/jn.1989.61.2.374. [DOI] [PubMed] [Google Scholar]
  30. Sterling P. Microcircuitry of the cat retina. Annu Rev Neurosci. 1983;6:149–185. doi: 10.1146/annurev.ne.06.030183.001053. [DOI] [PubMed] [Google Scholar]
  31. Tauck D. L., Frosch M. P., Lipton S. A. Characterization of GABA- and glycine-induced currents of solitary rodent retinal ganglion cells in culture. Neuroscience. 1988 Oct;27(1):193–203. doi: 10.1016/0306-4522(88)90230-8. [DOI] [PubMed] [Google Scholar]
  32. Verdoorn T. A., Draguhn A., Ymer S., Seeburg P. H., Sakmann B. Functional properties of recombinant rat GABAA receptors depend upon subunit composition. Neuron. 1990 Jun;4(6):919–928. doi: 10.1016/0896-6273(90)90145-6. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES