Summary
-
1.
The effects of external sodium on GABA-induced chloride currents were examined with whole-cell voltage-clamp recordings obtained from enzymatically dissociated solitary Muller cells in culture. Our goal was to determine whether a sodium-dependent GABA uptake mechanism influences the GABAa-mediated responses of skate Muller cells.
-
2.
At low concentrations of GABA (0.01 to 0.5µM), removal of sodium from the external solution resulted in a marked increase in the ligand-gated currents mediated by activation of GABAa receptors. The enhancement by lowered sodium was greatest at hyperpolarizing potentials and decreased progressively as the cell was depolarized.
-
3.
The reversal potential for the GABA-induced response was not significantly altered by the removal of sodium, suggesting that sodium ions did not directly contribute to the GABAa-mediated current.
-
4.
Lowering external sodium had no effect on the currents induced by the GABAa-agonist muscimol, consistent with its much lower affinity for the GABA transport carrier.
-
5.
Application of the GABA uptake blocker nipecotic acid also abolished the effects of lowered sodium.
-
6.
These findings suggest that the effects of lowered external sodium resulted from a decrease in the uptake of GABA into the Muller cells, thus raising the effective concentration of GABA acting upon the GABAa receptors.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Akaike, N., Maruyama, T., Sikdar, S. K., and Yasui, S. (1987). Sodium-dependent suppression ofγ-aminobutyric acid-gated chloride currents in internally perfused frog sensory neurones.J. Physiol. 392543–562.
Barbour, B., Brew, H., and Attwell, D. (1991). Electrogenic uptake of glutamate and aspartate into glial cells isolated from the salamander (Ambystoma) retina.J. Physiol. 436169–193.
Bignami, A., and Dahl, D. (1979). The radial glia of Muller in the rat retina and their response to injury. An immunofluorescence study with antibodies to the glial acidic fibrillary (GFA) protein.Exp. Eye Res. 2863–69.
Brew, H., and Attwell, D. (1987). Electrogenic glutamate uptake is a major current carrier in the membrane of axolotl retinal glial cells.Nature 327707–709.
Brunken, W. J., Witkovsky, P., and Karten, H. (1986). Retinal neurochemistry of three elasmobranch species.J. Comp. Neurol. 2431–12.
Bruun, A., Ehinger, B., and Sytsma, V. M. (1984). Neurotransmitter localization in the skate retina.Brain Res. 295 233–248.
Conner, J. D., Detwiler, P. B., and Sarthy, P. V. (1985). Ionic and electrophysiological properties of retinal Muller (glial) cells of the turtle.J. Physiol. 36279–92.
DeFeudis, F. V. (1980). Binding studies with muscimol: Relation toγ-aminobutyrate receptors.Neuroscience 5675–688.
Desarmenien, M., Feltz, P., and Headley, P. M. (1980). Does glial uptake affect GABA responses? An intracellular study on rat dorsal root ganglion neuronesin vitro.J. Physiol. 307163–182.
Hamill, O. P., Marty, A., Neher, E., Sakmann, B., and Sigworth, F. J. (1981). Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches.Pflugers Arch. 39185–100.
Ishida, A. T., and Fain, G. L. (1981). D-aspartate potentiates the effects of 1-glutamate on horizontal cells in goldfish retina.Proc. Natl. Acad. Sci. USA 785890–5894.
Kanner, B. I. (1983). Bioenergetics of neurotransmitter transport.Biochim. Biophys. Acta 726293–316.
Keynan, S., and Kanner, B. I. (1988).γ-Aminobutyric acid transport in reconstituted preparations from rat brain: Coupled sodium and chloride fluxes.Biochemistry 2712–17.
Johnston, G. A. R., Curtis, D. R., Groat, W. C., and Duggan, A. W. (1968). Central action of ibotenic acid and muscimol.Biochem. Pharmacol. 172488–2489.
Lam, D. M. K. (1975). Synaptic chemistry of identified cells in the vertebrate retina.Cold Spring Harbor Symp. Quant. Biol. 40571–579.
Malchow, R. P., and Ripps, H. (1990). Effects ofγ-aminobutyric acid on skate retinal horizontal cells: Evidence for an electrogenic uptake mechanism.Proc. Natl. Acad. Sci. USA 878945–8949.
Malchow, R. P., Qian, H., and Ripps, H. (1989).γ-Aminobutyric acid (GABA)-induced currents of skate Muller (glial) cells are mediated by neuronal-like GABAA receptors.Proc. Natl. Acad. Sci. USA 864326–4330.
Martin, D. L. (1976). Carrier-mediated transport and removal of GABA from synaptic regions. InGABA in Nervous System Function (E. Roberts, T. N. Chase, and D. B. Tower, Eds.), Raven Press, New York, pp. 347–386.
Newman, E. A. (1988). Electrophysiology of retinal glial cells. InProgress in Retinal Research (N. N. Osborne, and G. J. Chader, Eds.), Pergamon Press, Oxford, pp. 153–171.
Puro, D. G. (1991). Stretch activated channels in human retinal Muller cells.Glia 4456–460.
Ripps, H., and Witkovsky, P. (1985). Neuron-glia interaction in the brain and retina. InProgress in Retinal Research (N. N. Osborne and G. J. Chader, Eds.) Pergamon Press, Oxford, pp. 181–220.
Sakai, S., Tasaka, J., and Tosaka, T. (1990). Sodium dependency of GABA uptake into glial cells in bullfrog sympathetic ganglia.Neurochem. Res. 15843–847.
Schousboe, A., Krogsgaard-Larsen, P., Svenneby, G., and Hertz, L. (1978). Inhibition of the high-affinity, net uptake of GABA into cultured astrocytes byβ-proline, nipecotic acid and other compounds.Brain Res. 153623–626.
Schwartz, E. A., and Tachibana, M. (1990). Electrophysiology of glutamate and sodium co-transport in a glial cell of the salamander retina.J. Physiol. 42643–80.
Sivilotti, T. (1988). Nipecotic acid enhances synaptic transmission in the frog optic tectum by an action independent of GABA uptake inhibition.Neurosci. Lett. 88107–112.
Snyder, S. H., Young, A. B., Bennet, J. P., and Mulder, A. H. (1973). Synaptic biochemistry of amino acids.Fed. Proc. 322039–2047.
Stockton, R. A., and Slaughter, M. M. (1991). Depolarizing actions of GABA and glycine on amphibian retinal horizontal cells.J. Neurophysiol. 65680–692.
Yazulla, S. (1986). GABAergic mechanisms in the retina. InProgress in Retinal Research (N. N. Osborne and G. J. Chader, Eds.), Pergamon Press, Oxford, pp. 1–52.
Yazulla, S., and Brecha, N. (1980). Binding and uptake of the GABA analogue,3H-muscimol, in the retinas of goldfish and chick.Invest. Ophthalmol. 191415–1425.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Qian, H., Malchow, R.P. & Ripps, H. The effects of lowered extracellular sodium onγ-aminobutyric acid (GABA)-induced currents of muller (glial) cells of the skate retina. Cell Mol Neurobiol 13, 147–158 (1993). https://doi.org/10.1007/BF00735371
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00735371