The neuroprotective KDI domain of gamma 1-laminin is a universal and potent inhibitor of ionotropic glutamate receptors

Previous work from this laboratory indicates that the KDI (Lys-Asp-Ile) domain of gamma 1-laminin promotes functional regeneration of adult rat spinal cord injuries and protects adult rat hippocampal neurons against massive neuronal death induced by intracerebral injection of the glutamate analogue...

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Veröffentlicht in:Journal of neuroscience research 2005-09, Vol.81 (6), p.797
Hauptverfasser: Möykkynen, Tommi, Liebkind, Ron, Sjöberg, Jari, Korpi, Esa R, Liesi, Päivi
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container_issue 6
container_start_page 797
container_title Journal of neuroscience research
container_volume 81
creator Möykkynen, Tommi
Liebkind, Ron
Sjöberg, Jari
Korpi, Esa R
Liesi, Päivi
description Previous work from this laboratory indicates that the KDI (Lys-Asp-Ile) domain of gamma 1-laminin promotes functional regeneration of adult rat spinal cord injuries and protects adult rat hippocampal neurons against massive neuronal death induced by intracerebral injection of the glutamate analogue kainic acid. In the present study, we used patch clamp recordings on cultured human embryonic neocortical neurons and HEK 293 cells expressing recombinant glutamate receptor subunits to study a putative interaction of the KDI with the glutamate system. We show that the KDI domain of gamma 1-laminin is a universal and potent inhibitor of AMPA, kainate, and NMDA subclasses of glutamate receptors, with a noncompetitive action on the AMPA receptor channel activity. Glutamate neurotoxicity plays a key role in both CNS trauma and neurodegenerative disorders, so this unexpected, novel function of the gamma 1-laminin-derived tripeptide may prove clinically valuable in treatment of CNS trauma and/or disease.
doi_str_mv 10.1002/jnr.20523
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In the present study, we used patch clamp recordings on cultured human embryonic neocortical neurons and HEK 293 cells expressing recombinant glutamate receptor subunits to study a putative interaction of the KDI with the glutamate system. We show that the KDI domain of gamma 1-laminin is a universal and potent inhibitor of AMPA, kainate, and NMDA subclasses of glutamate receptors, with a noncompetitive action on the AMPA receptor channel activity. 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subjects Cell Line
Cells, Cultured
Electrophysiology
Excitatory Amino Acid Antagonists
Humans
Immunohistochemistry
Laminin - pharmacology
Membrane Potentials - physiology
Nerve Regeneration - drug effects
Neurons - physiology
Neuroprotective Agents - pharmacology
Patch-Clamp Techniques
Receptors, AMPA - drug effects
Receptors, Glutamate - drug effects
Receptors, N-Methyl-D-Aspartate - drug effects
title The neuroprotective KDI domain of gamma 1-laminin is a universal and potent inhibitor of ionotropic glutamate receptors
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