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Ca 2+ permeability of the channel pore is not essential for the δ2 glutamate receptor to regulate synaptic plasticity and motor coordination
Author(s) -
Kakegawa Wataru,
Miyazaki Taisuke,
Hirai Hirokazu,
Motohashi Junko,
Mishina Masayoshi,
Watanabe Masahiko,
Yuzaki Michisuke
Publication year - 2007
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2006.127100
Subject(s) - glutamate receptor , nmda receptor , microbiology and biotechnology , long term depression , synaptic plasticity , cerebellum , chemistry , ampa receptor , synapse , transgene , genetically modified mouse , neuroscience , biophysics , biology , receptor , biochemistry , gene
The δ2 glutamate receptor (GluRδ2) plays a crucial role in cerebellar functions; mice with a disrupted GluR δ 2 gene ( GluR δ 2 −/− ) display impaired synapse formation and abrogated long‐term depression (LTD). However, the mechanisms by which GluRδ2 functions have remained unclear. Because a GluRδ2 mutation in lurcher mice causes channel activities characterized by Ca 2+ permeability, GluRδ2 was previously suggested to serve as a Ca 2+ ‐permeable channel in Purkinje cells. To test this hypothesis, we introduced a GluR δ 2 transgene, which had a mutation (Gln618Arg) in the putative channel pore, into GluR δ 2 −/− mice. Interestingly, the mutant transgene rescued the major functional and morphological abnormalities of GluR δ 2 −/− Purkinje cells, such as enhanced paired‐pulse facilitation, impaired LTD at parallel fibre synapses, and sustained innervation by multiple climbing fibres. These results indicate that the conserved glutamine residue in the channel pore, which is crucial for all Ca 2+ ‐permeable glutamate receptors, is not essential for the function of GluRδ2.