Skip to main content
×
Home
    • Aa
    • Aa

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

  • Donald G. Puro (a1), Joseph P. Yuan (a2) and Nikolaus J. Sucher (a2)
Abstract
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.

Copyright
Linked references
Hide All

This list contains references from the content that can be linked to their source. For a full set of references and notes please see the PDF or HTML where available.

E. Agardh , H.H. Yeh , R. Herrmann & D.G. Puro (1985). γ-aminobutyric acid-mediated inhibition at cholinergic synapses formed by cultured retinal neurons. Brain Research 330, 323328.

B. Barbour , H. Brew & D. Attwell (1988). Electrogenic glutamate uptake in glial cells is activated by intracellular potassium. Nature 335, 433435.

G.V. Blankenfeld & H. Kettenmann (1991). Glutamate and GABA receptors in vertebrate glial cells. Molecular Neurobiology 5, 3143.

J.H. brandstäTter , E. Hartveit , M. Sassoe-Pognetto & H. WÄSsle (1994). Expression of NMDA and high-affinity kainate receptor subunit mRNAs in the adult rat retina. European Journal of Neuroscience 6, 110112.

H. Brew , P.T.A. Gray , P. Mobbs & D. Atwell (1986). Endfeet of retinal glial cells have higher densities of ion channels that mediate K+ buffering. Nature 324, 466468.

T.L. Chao , A. Henke , W. Reichelt , W. Eberhardt , S. Reinhardt-Maelicke & A. Reichenbach (1994). Three distinct types of voltage-dependent K+ channels are expressed by Müller (glial) cells of the rabbit retina. Pflügers Archive 426, 5160.

D. Forrest , M. Yuzaki , H.D. Soares , L. Ng , D.C. Luk , M. Sherry , C.L. Stewar , J.I. Morgan , J.A. Connar & T. Curran (1994). Targeted disruption of NMDA receptor 1 gene abolishes NMDA response and results n neonatal death. Neuron 13, 325338.

R. Horn & S.J. Korn (1992). Prevention of rundown in electrophysiological recordings. Methods Enzymology 207, 149155.

T. Ikeda & D.G. Puro (1995). Truncation of IGF-I yield two mitogens for retinal Müller glial cells. Brain Research 686, 8792.

C.J. Karwoski , H.-K. LU & E.A. Newman (1989). Spatial buffering of light-evoked potassium increased by retinal Müller (glial) cells. Science 244, 528580.

G.P. Lewis , P.A. Erickson , D.D. Kaska & S.K. Fisher (1988). An immunocytochemical comparison of Müller cells and astrocytes in the cat retina. Experimental Eye Research, 47, 839853.

Y. Li , R.S. Erzurumlu , C. Chen , S. Jhaveri & J. Tonegawa (1994). Wisker-related neuronal patterns fail to develop in the trigemenal brainstem nuclei of NMDAR1 knockout mice. Cell 76, 427437.

D.R. Lucas & J.P. Newhouse (1957). The toxic effect of sodium L-glutamate on the inner layers of the retina. Archives of Ophthalmology 58, 193201.

J.M. Luque & J.G. Richards (1995). Expression of NMDA2B receptor subunit mRNA in Bergmann glia. Glia 13, 228232.

A.B. Macdermott & N. Dale (1987). Receptors, ion channels and synaptic potentials underlying the integrative actions of excitatory amino acids. Trends in Neuroscience 10, 280284.

S.C. Massey (1990). Cell types using glutamate as a neurotransmitters in the vertebrate retina. Progress in Retinal Research 9, 399425.

C. Matute & R. Miledi (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.

K. Moriyoshi , M. Masu , T. Ishii , R. Shigemoto , N. Mizuno & S. Nakaniski (1991). Molecular cloning and characterization of the rat NMDA receptor. Nature 354, 3137.

E.A. Newman , D.A. Framback & L.L. Odette (1984). Control of extracellular potassium levels by retinal glial cells K+ siphoning. Science 225, 11741175.

T.M. Nork , I.H.L. Wallow , S.J. Sranek & G. Anderson (1987). Müller's cell involvement in proliferative diabetic retinopathy. Archives of Ophthalmology 105, 14241429.

D.G. Puro (1991 a). Stretch-activated channels in human retinal Müller cells. Glia 4, 456460.

D.G. Puro (1991 b). A calcium-activated, calcium-permeable ion channel in human retinal glial cells: Modulation by basic fibroblast growth factor. Brain Research 548, 329333.

D.G. Puro (1994). Calcium channels of human retinal glial cells. In Methods in Neuroscience, Volume 19, ed. T. Narahaski , pp. 6881. Orlando, Florida: Academic Press.

D.G. Puro , T. Mano , C.-C. Chan , M. Fukuda & H. Shimada (1990). Thrombin stimulates the proliferation of human retinal glial cells. Graefe's Archives of Clinical Experimental Ophthalmology 228, 169173.

D.G. Puro & E.L. Stuenkel (1995). Thrombin-induced inhibition of potassium currents in human retinal glial (Müller) cells. Journal of Physiology (London) 485, 337348.

J. Rae , K. Cooper , P. Gates & M. Wesky (1991). Low access resistance perforated patch recordings using amphotericin B. Journal of Neuroscience Methods 37, 1526.

W. Reichelt , & T. Pannicke (1993). Voltage-dependent K+ currents in guinea pig Müller (glial) cells show different sensitivities to blockade by Ba2+. Neuroscience Letters 155, 1518.

M. Sarantis & D. Attwell (1990). Glutamate uptake in mammalian retinal glia is voltage-and potassium-dependent. Brain Research 516, 322325.

E.A. Schwartz (1993). L-Glutamate conditionally modulates the K+ current of Müller glial cells. Neuron 10, 11411149.

E.A. Schwartz & M. Tachibana (1990). Electrophysiology of glutamate and sodium co-transport in a glial cell of the salamander retina. Journal of Physiology (London) 426, 4380.

S.J. Siegel , N. Brose , W.G. Janssen , G.P. Gasic , R. John , S.F. Heinemann & J.H. Morrison (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.

A.M. Thompson (1989). Glycine modulation of the NMDA receptor/channel complex. Trends in Neuroscience 12, 349353.

Y. Uchihori & D.G. Puro (1993). Glutamate as a neuron-to-glial signal for mitogenesis: Role of glial N-methyl-D-aspartate receptors. Brain Research 613, 212220.

H. Wolburg & K. Berg (1988). Distribution of orthogonal arrays of particles in the Müller cell membrane of the mouse retina. Glia 1, 246252.

Recommend this journal

Email your librarian or administrator to recommend adding this journal to your organisation's collection.

Visual Neuroscience
  • ISSN: 0952-5238
  • EISSN: 1469-8714
  • URL: /core/journals/visual-neuroscience
Please enter your name
Please enter a valid email address
Who would you like to send this to? *
×

Keywords:

Metrics

Full text views

Total number of HTML views: 0
Total number of PDF views: 10 *
Loading metrics...

Abstract views

Total abstract views: 115 *
Loading metrics...

* Views captured on Cambridge Core between September 2016 - 23rd May 2017. This data will be updated every 24 hours.