Hostname: page-component-7c8c6479df-p566r Total loading time: 0 Render date: 2024-03-28T23:46:58.628Z Has data issue: false hasContentIssue false

Activation of NMDA receptor-channels in human retinal Müller glial cells inhibits inward-rectifying potassium currents

Published online by Cambridge University Press:  02 June 2009

Donald G. Puro
Affiliation:
Departments of Ophthalmology and Physiology, University of Michigan, Ann Arbor
Joseph P. Yuan
Affiliation:
Department of Neurology, Children's Hospital, Harvard Medical School, Boston
Nikolaus J. Sucher
Affiliation:
Department of Neurology, Children's Hospital, Harvard Medical School, Boston

Abstract

Although it is well known that neurotransmitters mediate neuron-to-neuron communication, it is becoming clear that neurotransmitters also affect glial cells. However, knowledge of neuron-to-glial signalling is limited. In this study, we examined the effects of the glutamate agonist N-methyl-D-aspartate (NMDA) on Müller cells, the predominant glia of the retina. Our immunocytochemical studies and immunodetection by Western blotting with monoclonal antibodies specific for the NMDAR1 subunit provided evidence for the expression by human Müller cells of this essential component of NMDA receptor-channels. Under conditions in which potassium currents were blocked, NMDA-induced currents could be detected in perforated-patch recordings from cultured and freshly dissociated human Müller cells. These currents were inhibited by competitive and non-competitive blockers of NMDA receptor-channels. Extracellular magnesium reduced the NMDA-activated currents in a voltage-dependent manner. However, despite a partial block by magnesium, Müller cells remained responsive to NMDA at the resting membrane potential. Under assay conditions not blocking K+ currents, exposure of Müller cells to NMDA was associated with an MK-801 sensitive inhibition of the inward-rectifying K+ current (IK(IR)), the largest current of these glia. This inhibitory effect of NMDA appears to be mediated by an influx of calcium since the inhibition of IK(IR) was significantly reduced when calcium was removed from the bathing solution or when the Müller cells contained the calcium chelator, BAPTA. Inhibition of the Müller cell KIR channels by the neurotransmitter glutamate is likely to have significant functional consequences for the retina since these ion channels are involved in K+ homeostasis, which in turn influences neuronal excitability.

Type
Research Articles
Copyright
Copyright © Cambridge University Press 1996

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.)

References

REFERENCES

Agardh, E., Yeh, H.H., Herrmann, R. & Puro, D.G. (1985). γ-aminobutyric acid-mediated inhibition at cholinergic synapses formed by cultured retinal neurons. Brain Research 330, 323328.Google Scholar
Akopian, A. & Witkovsky, P. (1995). Dopamine modulates distinct hyperpolarization activated currents in rods and glial cells. Investigative Ophthalmology and Visual Science 36, S289.Google Scholar
Barbour, B., Brew, H. & Attwell, D. (1988). Electrogenic glutamate uptake in glial cells is activated by intracellular potassium. Nature 335, 433435.Google Scholar
Biedermann, B., Frohlich, E., Grosche, J., Wagner, H.-J. & Reichenbach, A. (1995). Mammalian Müller (glial) cells express functional D2 dopamine receptors. Neuro Report 6, 609612.Google Scholar
Blankenfeld, G.V. & Kettenmann, H. (1991). Glutamate and GABA receptors in vertebrate glial cells. Molecular Neurobiology 5, 3143.Google Scholar
brandstäTter, J.H., Hartveit, E., Sassoe-Pognetto, M. & WÄSsle, H. (1994). Expression of NMDA and high-affinity kainate receptor subunit mRNAs in the adult rat retina. European Journal of Neuroscience 6, 110112.Google Scholar
Brew, H., Gray, P.T.A., Mobbs, P. & Atwell, D. (1986). Endfeet of retinal glial cells have higher densities of ion channels that mediate K+ buffering. Nature 324, 466468.Google Scholar
Chan, C.-C., Rosenszajn, L.A., Nussenblatt, R.B., Mullenberg-Coulombre, C., Hsu, S.-M., Palestine, A.G., Lando, Z. & Benezra, D. (1984). Monoclonal antibodies to Müller cells of the retina. Investigative Ophthalmology and Visual Science 25, 10081012.Google Scholar
Chao, T.L., Henke, A., Reichelt, W., Eberhardt, W., Reinhardt-Maelicke, S. & Reichenbach, A. (1994). Three distinct types of voltage-dependent K+ channels are expressed by Müller (glial) cells of the rabbit retina. Pflügers Archive 426, 5160.Google Scholar
Fisher, S.K. & Anderson, D.H. (1994). Cellular effects of detachment on the neural retina and the retinal pigment epithelium. In Retina ed., Ryan, S.J., pp. 20352061. St. Louis, Missouri: Mosby.Google Scholar
Forrest, D., Yuzaki, M., Soares, H.D., Ng, L., Luk, D.C., Sherry, M., Stewar, C.L., Morgan, J.I., Connar, J.A. & Curran, T. (1994). Targeted disruption of NMDA receptor 1 gene abolishes NMDA response and results n neonatal death. Neuron 13, 325338.Google Scholar
Gonoi, T., Mizuno, N., Inagaki, N., Kuromi, H., Seino, Y., Moyazaki, J. & Seino, S. (1994). Functional neuronal ionotrophic glutamate receptors are expressed in the non-neuronal cell line MIG. Journal Biology Chemistry 269, 1698916992.Google Scholar
Horn, R. & Korn, S.J. (1992). Prevention of rundown in electrophysiological recordings. Methods Enzymology 207, 149155.Google Scholar
Ikeda, T. & Puro, D.G. (1995). Truncation of IGF-I yield two mitogens for retinal Müller glial cells. Brain Research 686, 8792.Google Scholar
Karwoski, C.J., LU, H.-K. & Newman, E.A. (1989). Spatial buffering of light-evoked potassium increased by retinal Müller (glial) cells. Science 244, 528580.Google Scholar
Lewis, G.P., Erickson, P.A., Kaska, D.D. & Fisher, S.K. (1988). An immunocytochemical comparison of Müller cells and astrocytes in the cat retina. Experimental Eye Research, 47, 839853.Google Scholar
Li, Y., Erzurumlu, R.S., Chen, C., Jhaveri, S. & Tonegawa, J. (1994). Wisker-related neuronal patterns fail to develop in the trigemenal brainstem nuclei of NMDAR1 knockout mice. Cell 76, 427437.Google Scholar
Lucas, D.R. & Newhouse, J.P. (1957). The toxic effect of sodium L-glutamate on the inner layers of the retina. Archives of Ophthalmology 58, 193201.Google Scholar
Luque, J.M. & Richards, J.G. (1995). Expression of NMDA2B receptor subunit mRNA in Bergmann glia. Glia 13, 228232.Google Scholar
Macdermott, A.B. & Dale, N. (1987). Receptors, ion channels and synaptic potentials underlying the integrative actions of excitatory amino acids. Trends in Neuroscience 10, 280284.Google Scholar
Massey, S.C. (1990). Cell types using glutamate as a neurotransmitters in the vertebrate retina. Progress in Retinal Research 9, 399425.Google Scholar
Matute, C. & Miledi, R. (1993). Neurotransmitter receptors and voltage-dependent Ca2+ channels encoded by mRNA from the adult corpus callosum. Proceedings of the National Academy of Sciences of the U.S.A. 90, 32703274.Google Scholar
Moriyoshi, K., Masu, M., Ishii, T., Shigemoto, R., Mizuno, N. & Nakaniski, S. (1991). Molecular cloning and characterization of the rat NMDA receptor. Nature 354, 3137.Google Scholar
MüLler, T., Grosehe, J., Ohlemeyer, C. & Kettenmann, H. (1993). NMDA-activated currents in Bergmann glial cells. Neuro Report 4, 671674.Google Scholar
Newman, E.A. (1985). Membrane physiology of retinal glial (Müller) cells. Journal of Neuroscience 5, 22252239.Google Scholar
Newman, E.A. (1993). Inward-rectifying potassium channels in retinal glial (Müller) cells. Journal of Neuroscience 13, 33333345.Google Scholar
Newman, E.A., Framback, D.A. & Odette, L.L. (1984). Control of extracellular potassium levels by retinal glial cells K+ siphoning. Science 225, 11741175.Google Scholar
Nork, T.M., Wallow, I.H.L., Sranek, S.J. & Anderson, G. (1987). Müller's cell involvement in proliferative diabetic retinopathy. Archives of Ophthalmology 105, 14241429.Google Scholar
Olney, J.W. (1988). Endogenous excitotoxins and neuropathological disorders. In Excitatory Amino Acids in Health and Disease, ed. Lode, D., pp. 337351. New York: John Wiley & Son.Google Scholar
Puro, D.G. (1991 a). Stretch-activated channels in human retinal Müller cells. Glia 4, 456460.Google Scholar
Puro, D.G. (1991 b). A calcium-activated, calcium-permeable ion channel in human retinal glial cells: Modulation by basic fibroblast growth factor. Brain Research 548, 329333.Google Scholar
Puro, D.G. (1994). Calcium channels of human retinal glial cells. In Methods in Neuroscience, Volume 19, ed. Narahaski, T., pp. 6881. Orlando, Florida: Academic Press.Google Scholar
Puro, D.G. (in press). Growth factors and Müller cells. Progress in Retinal and Eye Research 15.Google Scholar
Puro, D.G. & Mano, T. (1991). Modulation of calcium channels in human retinal glial cells by basic fibroblast growth factor: A possible role in retinal pathobiology. Journal of Neuroscience 11, 18731880.Google Scholar
Puro, D.G., Mano, T., Chan, C.-C., Fukuda, M. & Shimada, H. (1990). Thrombin stimulates the proliferation of human retinal glial cells. Graefe's Archives of Clinical Experimental Ophthalmology 228, 169173.Google Scholar
Puro, D.G. & Stuenkel, E.L. (1995). Thrombin-induced inhibition of potassium currents in human retinal glial (Müller) cells. Journal of Physiology (London) 485, 337348.Google Scholar
Rae, J., Cooper, K., Gates, P. & Wesky, M. (1991). Low access resistance perforated patch recordings using amphotericin B. Journal of Neuroscience Methods 37, 1526.Google Scholar
Reichelt, W., & Pannicke, T. (1993). Voltage-dependent K+ currents in guinea pig Müller (glial) cells show different sensitivities to blockade by Ba2+. Neuroscience Letters 155, 1518.Google Scholar
Sarantis, M. & Attwell, D. (1990). Glutamate uptake in mammalian retinal glia is voltage-and potassium-dependent. Brain Research 516, 322325.Google Scholar
Schwartz, E.A. (1993). L-Glutamate conditionally modulates the K+ current of Müller glial cells. Neuron 10, 11411149.Google 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 (London) 426, 4380.Google Scholar
Siegel, S.J., Brose, N., Janssen, W.G., Gasic, G.P., John, R., Heinemann, S.F. & Morrison, J.H. (1994). Regional, cellular and ultrastructural distribution of N-methyl-D-aspartate receptor subunit 1 in monkey hippocampus. Proceedings of the National Academy of Sciences of the U.S.A. 91, 564568.Google Scholar
Sucher, N.J., Brose, N., Deitcher, D.L., Awobuluyi, M., Gasic, G.P., Bading, H., Cepko, C.L., Greenberg, M.E., John, R., Heinemann, S.F. & Lipton, S.A. (1993). Expression of endogenous NMDAR1 transcripts without receptor protein suggests post-transcriptional control in PC12 cells. Journal of Biological Chemistry 268, 2229922304.Google Scholar
Thompson, A.M. (1989). Glycine modulation of the NMDA receptor/channel complex. Trends in Neuroscience 12, 349353.Google Scholar
Uchihori, Y. & Puro, D.G. (1993). Glutamate as a neuron-to-glial signal for mitogenesis: Role of glial N-methyl-D-aspartate receptors. Brain Research 613, 212220.Google Scholar
Wolburg, H. & Berg, K. (1988). Distribution of orthogonal arrays of particles in the Müller cell membrane of the mouse retina. Glia 1, 246252.Google Scholar