Hostname: page-component-669899f699-ggqkh Total loading time: 0 Render date: 2025-04-25T14:46:21.770Z Has data issue: false hasContentIssue false
  • English
  • Français

Activation of glutamate transporters in rods inhibits presynaptic calcium currents

Published online by Cambridge University Press:  23 January 2004

KATALIN RABL ,
ERIC J. BRYSON  and
WALLACE B. THORESON
KATALIN RABL
Affiliation:
Department of Ophthalmology, University of Nebraska Medical Center, Omaha On leave from the Department of General Zoology and Neurobiology, University of Pécs, Pécs, Hungary
ERIC J. BRYSON
Affiliation:
Department of Ophthalmology, University of Nebraska Medical Center, Omaha
WALLACE B. THORESON
Affiliation:
Department of Ophthalmology, University of Nebraska Medical Center, Omaha Department of Pharmacology, University of Nebraska Medical Center, Omaha
Get access Rights & Permissions [Opens in a new window]

Abstract

We found that L-glutamate (L-Glu) inhibits L-type Ca2+ currents (ICa) in rod photoreceptors. This inhibition was studied in isolated rods or rods in retinal slices from tiger salamander using perforated patch whole cell recordings and Cl−-imaging techniques. Application of L-Glu inhibited ICa by ∼20% at 0.1 mM and ∼35% at 1 mM. L-Glu also produced an inward current that reversed around ECl. The metabotropic glutamate receptor (mGluR) agonists t-ADA (Group I), DCG-IV (Group II), and L-AP4 (Group III) had no effect on ICa. However, the glutamate transport inhibitor, TBOA (0.1 mM), prevented L-Glu from inhibiting ICa. D-aspartate (D-Asp), a glutamate transporter substrate, also inhibited ICa with significantly more inhibition at 1 mM than 0.1 mM. Using Cl− imaging, L-Glu (0.1–1 mM) and D-Asp (0.1–1 mM) were found to stimulate a Cl− efflux from terminals of isolated rods whereas the ionotropic glutamate receptor agonists NMDA, AMPA, and kainate and the mGluR agonist, 1S,3R-ACPD, did not. Glutamate-evoked Cl− effluxes were blocked by the glutamate transport inhibitors TBOA and DHKA. Cl− efflux inhibits Ca2+ channel activity in rod terminals (Thoreson et al. (2000), Visual Neuroscience17, 197). Consistent with the possibility that glutamate-evoked Cl− efflux may play a role in the inhibition, reducing intraterminal Cl− prevented L-Glu from inhibiting ICa. In summary, the results indicate that activation of glutamate transporters inhibits ICa in rods possibly as a consequence of Cl− efflux. The neurotransmitter L-Glu released from rod terminals might thus provide a negative feedback signal to inhibit further L-Glu release.

Keywords

PhotoreceptorL-type calcium channelRetinaGlutamate transporterTiger salamander
Type
Research Article
Information
Visual Neuroscience , Volume 20 , Issue 5 , September 2003 , pp. 557 - 566
Copyright
2003 Cambridge University Press

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

REFERENCES

Arriza, J.L., Fairman, W.A., Wadiche, J.I., Murdoch, G.H., Kavanaugh, M.P., & Amara, S.G. (1994). Functional comparisons of three glutamate transporter subtypes cloned from human motor cortex. Journal of Neuroscience 14, 5559–5569Google Scholar
Arriza, J.L., Eliasof, S., Kavanaugh, M.P., & Amara, S.G. (1997). Excitatory amino acid transporter 5, a retinal glutamate transporter coupled to a chloride conductance. Proceedings of the National Academy of Sciences of the U. S. A. 94, 4155–4160.CrossRefGoogle Scholar
Ayoub, G.S. & Copenhagen, D.R. (1991). Application of a fluorometric method to measure glutamate release from single retinal photoreceptors. Journal of Neuroscience Methods 37, 7–14.CrossRefGoogle Scholar
Barbour, B., Brew, H., & Attwell, D. (1991). Electrogenic uptake of glutamate and aspartate into glial cells isolated from the salamander (Ambystoma) retina. Journal of Physiology 436, 169–193.CrossRefGoogle Scholar
Barnes, S. & Hille, B. (1989). Ionic channels of the inner segment of tiger salamander cone photoreceptors. Journal of General Physiology 94, 719–743.CrossRefGoogle Scholar
Biwersi, J. & Verkman, A.S. (1991). Cell-permeable fluorescent indicator for cytosolic chloride. Biochemistry 30, 7879–7883.CrossRefGoogle Scholar
Brew, H. & Attwell, D. (1987). Electrogenic glutamate uptake is a major current carrier in the membrane of axolotl retinal glial cells. Nature 327, 707–709.CrossRefGoogle Scholar
Burkhardt, D.A., Gottesman, J., & Thoreson, W.B. (1988). Prolonged depolarization in turtle cones evoked by current injection and stimulation of the receptive field surround. Journal of Physiology 407, 329–348.CrossRefGoogle Scholar
Burkhardt, D.A., Zhang, S.Q., & Gottesman, J. (1991). Prolonged depolarization in rods in situ. Visual Neuroscience 6, 607–614.CrossRefGoogle Scholar
Copenhagen, D.R. & Jahr, C.E. (1989). Release of endogenous excitatory amino acids from turtle photoreceptors. Nature 341, 536–539.CrossRefGoogle Scholar
Danbolt, N.C. (2001). Glutamate uptake. Progress in Neurobiology 65, 1–105.CrossRefGoogle Scholar
Dixon, D.B., Takahashi, K., & Copenhagen, D.R. (1993). L-glutamate suppresses HVA calcium current in catfish horizontal cells by raising intracellular proton concentration. Neuron 11, 267–277.CrossRefGoogle Scholar
Ebihara, S., Shirato, K., Harata, N., & Akaike, N. (1995). Gramicidin-perforated patch recording: GABA response in mammalian neurones with intact intracellular chloride. Journal of Physiology 484, 77–86.CrossRefGoogle Scholar
Eliasof, S. & Werblin, F. (1993). Characterization of the glutamate transporter in retinal cones of the tiger salamander. Journal of Neuroscience 13, 402–411.Google Scholar
Eliasof, S., Arriza, J.L., Leighton, B.H., Kavanaugh, M.P., & Amara, S.G. (1998a). Excitatory amino acid transporters of the salamander retina: Identification, localization, and function. Journal of Neuroscience 18, 698–712.Google Scholar
Eliasof, S., Arriza, J.L., Leighton, B.H., Amara, S.G., & Kavanaugh, M.P. (1998b). Localization and function of five glutamate transporters cloned from the salamander retina. Vision Research 38, 1443–1454.Google Scholar
Fain, G.L., Quandt, F.N., & Gerschenfeld, H.M. (1977). Calcium-dependent regenerative responses in rods. Nature 269, 707–710.CrossRefGoogle Scholar
Fairman, W.A. & Amara, S.G. (1999). Functional diversity of excitatory amino acid transporters: Ion channel and transport modes. American Journal of Physiology 277, F481–F486.Google Scholar
Gaal, L., Roska, B., Picaud, S.A., Wu, S.M., Marc, R., & Werblin, F.S. (1998). Postsynaptic response kinetics are controlled by a glutamate transporter at cone photoreceptors. Journal of Neurophysiology 79, 190–196.Google Scholar
Grant, G.B. & Dowling, J.E. (1996). On bipolar cell responses in the teleost retina are generated by two distinct mechanisms. Journal of Neurophysiology 76, 3842–3849.Google Scholar
Grant, G.B. & Werblin, F.S. (1996). A glutamate-elicited chloride current with transporter-like properties in rod photoreceptors of the tiger salamander. Visual Neuroscience 13, 135–144.CrossRefGoogle Scholar
Haase, W., Friese, W., Gordon, R.D., Muller, H., & Cook, N.J. (1990). Immunological characterization and localization of the Na+/Ca2+-exchanger in bovine retina. Journal of Neuroscience 10, 1486–1494.Google Scholar
Harada, T., Harada, C., Watanabe, M., Inoue, Y., Sakagawa, T., Nakayama, N., Sasaki, S., Okuyama, S., Watase, K., Wada, K., & Tanaka, K. (1998). Functions of the two glutamate transporters GLAST and GLT-1 in the retina. Proceedings of the National Academy of Sciences of the U. S. A. 95, 4663–4666.CrossRefGoogle Scholar
Helmchen, F. (2000). Calibration of fluorescent calcium indicators. In Imaging Neurons: A Laboratory Manual, ed. Yuste, R., Lanni, F. & Konnerth, A., pp. 32.1–32.9. New York: Cold Spring Harbor Laboratory Press.
Higgs, M.H. & Lukasiewicz, P.D. (2002). Activation of group II metabotropic glutamate receptors inhibits glutamate release from salamander retinal photoreceptors. Visual Neuroscience 19, 275–281.CrossRefGoogle Scholar
Kaneko, A. & Tachibana, M. (1986). Effects of gamma-aminobutyric acid on isolated cone photoreceptors of hte turtle retina. Journal of Physiology 373, 443–461.CrossRefGoogle Scholar
Kanner, B.I. & Borre, L. (2002). The dual-function glutamate transporters: Structure and molecular characterisation of the substrate-binding sites. Biochimica Biophysica Acta 1555, 92–95.CrossRefGoogle Scholar
Kim, T.S., Reid, D.M., & Molday, R.S. (1998). Structure–function relationships and localization of the Na/Ca-K exchanger in rod photoreceptors. Journal of Biological Chemistry 273, 16561–16567.CrossRefGoogle Scholar
Krizaj, D. & Copenhagen, D.R. (1998). Compartmentalization of calcium extrusion mechanisms in the outer and inner segments of photoreceptors. Neuron 21, 249–256.CrossRefGoogle Scholar
Kourennyi, D.E. & Barnes, S. (2000). Depolarization-induced calcium channel facilitation in rod photoreceptors is independent of G-proteins and phosphorylation. Journal of Neurophysiology 84, 133–138.Google Scholar
Kyrozis, A. & Reichling, D.B. (1995). Perforated-patch recording with gramicidin avoids artifactual changes in intracellular chloride concentration. Journal of Neuroscience Methods 57, 27–35.CrossRefGoogle Scholar
Larsson, H.P., Picaud, S.A., Werblin, F.S., & Lecar, H. (1996). Noise analysis of the glutamate-activated current in photoreceptors. Biophysical Journal 70, 733–742.CrossRefGoogle Scholar
Otis, T.S. & Jahr, C.E. (1998). Anion currents and predicted glutamate flux through a neuronal glutamate transporter. Journal of Neuroscience 18, 7099–7110.Google Scholar
Owen, W.G. (1987). Ionic conductances in rod photoreceptors. Annual Review of Physiology 49, 743–764.CrossRefGoogle Scholar
Picaud, S., Larsson, H.P., Wellis, D.P., Lecar, H., & Werblin, F. (1995a). Cone photoreceptors respond to their own glutamate release in the tiger salamander. Proceedings of the National Academy of Sciences of the U. S. A. 92, 9417–9421.Google Scholar
Picaud, S.A., Larsson, H.P., Grant, G.B., Lecar, H., & Werblin, F.S. (1995b). Glutamate-gated chloride channel with glutamate-transporter-like properties in cone photoreceptors of the tiger salamander. Journal of Neurophysiology 74, 1760–1771.Google Scholar
Piccolino, M. & Gerschenfeld, H.M. (1980). Characteristics and ionic processes involved in feedback spikes of turtle cones. Proceedings of the Royal Society B (London) 206, 439–463.CrossRefGoogle Scholar
Pow, D.V. & Barnett, N.L. (2000). Developmental expression of excitatory amino acid transporter 5: A photoreceptor and bipolar cell glutamate transporter in rat retina. Neuroscience Letters 280, 21–24.CrossRefGoogle Scholar
Rabl, K. & Thoreson, W.B. (2002). Calcium-dependent inactivation and depletion of synaptic cleft calcium ions combine to regulate rod calcium currents under physiological conditions. European Journal of Neuroscience 16, 2070–2077.CrossRefGoogle Scholar
Rae, J., Cooper, K., Gates, P., & Watsky, M. (1991). Low access resistance perforated patch recordings using amphotericin B. Journal of Neuroscience Methods 37, 15–26.CrossRefGoogle Scholar
Schmitz, Y. & Witkovsky, P. (1997). Dependence of photoreceptor glutamate release on a dihydropyridine-sensitive calcium channel. Neuroscience 78, 1209–1216.CrossRefGoogle Scholar
Schwartz, E.A. & Tachibana, M. (1990). Electrophysiology of glutamate and sodium co-transport in a glial cell of the salamander retina. Journal of Physiology 426, 43–80.CrossRefGoogle Scholar
Shigeri, Y., Shimamoto, K., Yasuda-Kamatani, Y., Seal, R.P., Yumoto, N., Nakajima, T., & Amara, S.G. (2001). Effects of threo-beta-hydroxyaspartate derivatives on excitatory amino acid transporters (EAAT4 and EAAT5). Journal of Neurochemistry 79, 297–302.Google Scholar
Shimamoto, K., Lebrun, B., Yasuda-Kamatani, Y., Sakaitani, M., Shigeri, Y., Yumoto, N., & Nakajima, T. (1998). DL-threo-beta-benzyloxyaspartate, a potent blocker of excitatory amino acid transporters. Molecular Pharmacology 53, 195–201.Google Scholar
Stella, S.L., Bryson, E.J., & Thoreson, W.B. (2002). A2 adenosine receptors inhibit calcium influx through L-type calcium channels in rod photoreceptors of the salamander retina. Journal of Neurophysiology 87, 351–360.CrossRefGoogle Scholar
Tachibana, M. & Kaneko, A. (1988). L-glutamate-induced depolarization in solitary photoreceptors: A process that may contribute to the interaction between photoreceptors in situ. Proceedings of the National Academy of Sciences of the U. S. A. 85, 5315–5319.CrossRefGoogle Scholar
Thoreson, W.B. & Stella, S.L., Jr. (2000). Anion modulation of calcium current voltage dependence and amplitude in salamander rods. Biochimica Biophysica Acta 1464, 142–150.CrossRefGoogle Scholar
Thoreson, W.B., Nitzan, R., & Miller, R.F. (1997). Reducing extracellular Cl− suppresses dihydropyridine-sensitive Ca2+ currents and synaptic transmission in amphibian photoreceptors. Journal of Neurophysiology 77, 2175–2190.Google Scholar
Thoreson, W.B., Nitzan, R., & Miller, R.F. (2000). Chloride efflux inhibits single calcium channel open probability in vertebrate photoreceptors: Chloride imaging and cell-attached patch-clamp recordings. Visual Neuroscience 17, 197–206.Google Scholar
Thoreson, W.B., Stella, S.L., Jr., Bryson, E.J., Clements, J., & Witkovsky, P. (2002). D2-like dopamine receptors promote interactions between calcium and chloride channels that diminish rod synaptic transfer in the salamander retina. Visual Neuroscience 19, 235–247.CrossRefGoogle Scholar
Vandenbranden, C.A., Verweij, J., Kamermans, M., Muller, L.J., Ruijter, J.M., Vrensen, G.F., & Spekreijse, H. (1996). Clearance of neurotransmitter from the cone synaptic cleft in goldfish retina. Vision Research 36, 3859–3874.CrossRefGoogle Scholar
Wadiche, J.I., Amara, S.G., & Kavanaugh, M.P. (1995). Ion fluxes associated with excitatory amino acid transport. Neuron 15, 721–728.CrossRefGoogle Scholar
Werblin, F.S. (1978). Transmission along and between rods in the tiger salamander retina. Journal of Physiology 280, 449–470.CrossRefGoogle Scholar
Woll, E., Gschwentner, M., Furst, J., Hofer, S., Buemberger, G., Jungwirth, A., Frick, J., Deetjen, P., & Paulmichl, M. (1996). Fluorescence-optical measurements of chloride movements in cells using the membrane-permeable dye diH-MEQ. Pflugers Archiv 432, 486–493.CrossRefGoogle Scholar
Wu, S.M. (1987). Synaptic connections between neurons in living slices of the larval tiger salamander retina. Journal of Neuroscience Methods 20, 139–149.CrossRefGoogle Scholar
Yang, X.L. & Wu, S.M. (1997). Response sensitivity and voltage gain of the rod- and cone-bipolar cell synapses in dark-adapted tiger salamander retina. Journal of Neurophysiology 78, 2662–2673.Google Scholar