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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 Aug 15;88(16):7135–7139. doi: 10.1073/pnas.88.16.7135

Inhibition of calcium influx and calcium current by gamma-aminobutyric acid in single synaptic terminals.

R Heidelberger 1, G Matthews 1
PMCID: PMC52248  PMID: 1651495

Abstract

Inhibition of Ca influx and Ca current by gamma-aminobutyric acid (GABA) was studied in single synaptic terminals of isolated retinal bipolar neurons. Measurements of intracellular Ca concentration [( Ca]i) using the fluorescent Ca indicator fura-2 showed that GABA potently inhibited Ca influx into the terminal elicited by high extracellular K concentration ([K]o). This inhibition was attributed to GABA type A (GABAA) receptor-activated chloride ion conductance that prevented bipolar neurons from depolarizing sufficiently to activate the Ca current, even in response to increased [K]o. Patch-clamp recordings of the Ca current revealed a second effect of GABA: GTP-dependent inhibition of the Ca current. This inhibition was not mediated by GABAA receptors, but baclofen, which binds to the GABA type B (GABAB) receptor and is known to inhibit the Ca current in other systems, was not able to mimic the action of GABA. This suggests the involvement of a different type of GABAB-like receptor in the inhibition of Ca current by GABA. GABA did not cause an overall suppression of the Ca current; rather, the voltage-dependence of Ca-channel activation was shifted to more depolarized potentials. Thus, maximal inhibition of the Ca current by GABA occurred in the physiological range of potential.

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Selected References

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  1. 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]
  2. Dolphin A. C. G protein modulation of calcium currents in neurons. Annu Rev Physiol. 1990;52:243–255. doi: 10.1146/annurev.ph.52.030190.001331. [DOI] [PubMed] [Google Scholar]
  3. Drew C. A., Johnston G. A., Weatherby R. P. Bicuculline-insensitive GABA receptors: studies on the binding of (-)-baclofen to rat cerebellar membranes. Neurosci Lett. 1984 Dec 21;52(3):317–321. doi: 10.1016/0304-3940(84)90181-2. [DOI] [PubMed] [Google Scholar]
  4. Dunlap K., Fischbach G. D. Neurotransmitters decrease the calcium conductance activated by depolarization of embryonic chick sensory neurones. J Physiol. 1981 Aug;317:519–535. doi: 10.1113/jphysiol.1981.sp013841. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Elmslie K. S., Zhou W., Jones S. W. LHRH and GTP-gamma-S modify calcium current activation in bullfrog sympathetic neurons. Neuron. 1990 Jul;5(1):75–80. doi: 10.1016/0896-6273(90)90035-e. [DOI] [PubMed] [Google Scholar]
  6. Grynkiewicz G., Poenie M., Tsien R. Y. A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem. 1985 Mar 25;260(6):3440–3450. [PubMed] [Google Scholar]
  7. 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]
  8. Ishida A. T., Stell W. K., Lightfoot D. O. Rod and cone inputs to bipolar cells in goldfish retina. J Comp Neurol. 1980 Jun;191(3):315–335. doi: 10.1002/cne.901910302. [DOI] [PubMed] [Google Scholar]
  9. 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]
  10. Marc R. E., Stell W. K., Bok D., Lam D. M. GABA-ergic pathways in the goldfish retina. J Comp Neurol. 1978 Nov 15;182(2):221–244. doi: 10.1002/cne.901820204. [DOI] [PubMed] [Google Scholar]
  11. Saito T., Kondo H., Toyoda J. I. Ionic mechanisms of two types of on-center bipolar cells in the carp retina. I. The responses to central illumination. J Gen Physiol. 1979 Jan;73(1):73–90. doi: 10.1085/jgp.73.1.73. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Saito T., Kujiraoka T., Yonaha T. Connections between photoreceptors and horseradish peroxidase-injected bipolar cells in the carp retina. Vision Res. 1983;23(4):353–362. doi: 10.1016/0042-6989(83)90082-2. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. Tachibana M. Ionic currents of solitary horizontal cells isolated from goldfish retina. J Physiol. 1983 Dec;345:329–351. doi: 10.1113/jphysiol.1983.sp014981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Tachibana M., Kaneko A. gamma-Aminobutyric acid exerts a local inhibitory action on the axon terminal of bipolar cells: evidence for negative feedback from amacrine cells. Proc Natl Acad Sci U S A. 1987 May;84(10):3501–3505. doi: 10.1073/pnas.84.10.3501. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Tsien R. W., Lipscombe D., Madison D. V., Bley K. R., Fox A. P. Multiple types of neuronal calcium channels and their selective modulation. Trends Neurosci. 1988 Oct;11(10):431–438. doi: 10.1016/0166-2236(88)90194-4. [DOI] [PubMed] [Google Scholar]
  17. Yazulla S., Studholme K. M., Wu J. Y. GABAergic input to the synaptic terminals of mb1 bipolar cells in the goldfish retina. Brain Res. 1987 May 19;411(2):400–405. doi: 10.1016/0006-8993(87)91095-x. [DOI] [PubMed] [Google Scholar]

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