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  The lurcher mutation identifies delta2 as an AMPA/kainate receptor-like channel that is potentiated by Ca2+

Wollmuth, L. P., Kuner, T., Jatzke, C., Seeburg, P. H., Heintz, N., & Zuo, J. (2000). The lurcher mutation identifies delta2 as an AMPA/kainate receptor-like channel that is potentiated by Ca2+. The Journal of Neuroscience: the Official Journal of the Society for Neuroscience, 20(16), 5973-5980. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/10934245.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-2F01-0 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-2F04-A
Genre: Journal Article
Alternative Title : The lurcher mutation identifies delta2 as an AMPA/kainate receptor-like channel that is potentiated by Ca2+

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 Creators:
Wollmuth, Lonnie P.1, Author              
Kuner, Thomas1, 2, Author              
Jatzke, Claudia, Author
Seeburg, Peter H.2, Author              
Heintz, Nathaniel, Author
Zuo, Jian, Author
Affiliations:
1Department of Cell Physiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497701              
2Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society, ou_1497704              

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Free keywords: glutamate receptors; δ2; Lurcher mutation; polyamine block; Ca2+ permeability; fractional Ca2+ currents
 Abstract: Neurodegeneration in Lurcher (Lc) mice results from constitutive activation of delta 2, a subunit of ionotropic glutamate receptors (GluRs) with unknown natural ligands and channel properties. Homo-oligomeric channels of GluR-delta2 with the Lurcher mutation (GluR-delta 2(Lc)) expressed in human embryonic kidney 293 cells showed a doubly rectifying current-voltage relation reminiscent of the block by intracellular polyamines in AMPA/kainate channels. Similarly, the fraction of the total current carried by Ca(2+) was approximately 2-3%, comparable with that found in Ca(2+)-permeable AMPA/kainate channels. Currents through GluR-delta 2(Lc) channels were also potentiated by extracellular Ca(2+) in a biphasic manner, with maximal potentiation occurring at physiological concentrations of Ca(2+). We examined the functional role of the Q/R site in GluR-delta 2(Lc) by replacing glutamine with arginine. Analogous to AMPA/kainate receptors, GluR-delta 2(Lc)(R) channels showed no voltage-dependent block by intracellular polyamines and were nominally impermeable to Ca(2+). The potentiation by Ca(2+), however, remained intact. Hence, GluR-delta 2(Lc) channels are functionally similar to the AMPA/kainate receptor channels, consistent with the high-sequence identity shared by these subunits within the channel-lining M2 and M3 segments. Furthermore, potentiation by Ca(2+) and a permeability to Ca(2+) comparable with that of AMPA/kainate receptors provide a possible cause for cell death in Lurcher mice and may contribute to cerebellar long-term depression under physiological conditions.

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Language(s): eng - English
 Dates: 2000-03-242000-03-282000-06-022000-08-15
 Publication Status: Published in print
 Pages: 8
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 Table of Contents: -
 Rev. Method: Peer
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Title: The Journal of Neuroscience : the Official Journal of the Society for Neuroscience
  Other : J. Neurosci.
Source Genre: Journal
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Publ. Info: Baltimore, MD : The Society
Pages: - Volume / Issue: 20 (16) Sequence Number: - Start / End Page: 5973 - 5980 Identifier: ISSN: 0270-6474
CoNE: https://pure.mpg.de/cone/journals/resource/954925502187_1