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The P2X7 receptor as a route for non‐exocytotic glutamate release: dependence on the carboxyl tail
Author(s) -
Cervetto Chiara,
Alloisio Susanna,
Frattaroli Daniela,
Mazzotta Maria Chiara,
Milanese Marco,
Gavazzo Paola,
Passalacqua Mario,
Nobile Mario,
Maura Guido,
Marcoli Manuela
Publication year - 2013
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12143
Subject(s) - glutamate receptor , receptor , extracellular , exocytosis , microbiology and biotechnology , hek 293 cells , glutamic acid , biology , metabotropic glutamate receptor 6 , metabotropic glutamate receptor 1 , metabotropic glutamate receptor 7 , cysteine , nmda receptor , metabotropic glutamate receptor , biochemistry , chemistry , amino acid , membrane , enzyme
P2X7 receptors trigger Ca 2+ ‐dependent exocytotic glutamate release, but also function as a route for non‐exocytotic glutamate release from neurons or astrocytes. To gain an insight into the mechanisms involving the P2X7 receptor as a direct pathway for glutamate release, we compared the behavior of a full‐length rat P2X7 receptor, a truncated rat P2X7 receptor in which the carboxyl tail had been deleted, a rat P2X7 receptor with the 18‐amino acid cysteine‐rich motif of the carboxyl tail deleted, and a rat P2X2 receptor, all of which are expressed in HEK293 cells. We found that the P2X7 receptor function as a route for glutamate release was antagonized in a non‐competitive way by extracellular Mg 2+ , did not require the recruitment of pore‐forming molecules, and was dependent on the carboxyl tail. Indeed, the truncated P2X7 receptor and the P2X7 receptor with the deleted cysteine‐rich motif both lost their function as a pathway for glutamate release, while still evoking intracellular Ca 2+ elevation. No glutamate efflux was observed through the P2X2 receptor. Notably, HEK293 cells (lacking the machinery for Ca 2+ ‐dependent exocytosis), when transfected with P2X7 receptors, appear to be a suitable model for investigating the P2X7 receptor as a route for non‐exocytotic glutamate efflux.