The P2X7 receptor as a route for non‐exocytotic glutamate release: dependence on the carboxyl tail. (3rd February 2013)

• Record Type: Journal Article
• Authors: Cervetto, Chiara; Alloisio, Susanna; Frattaroli, Daniela; Mazzotta, Maria Chiara; Milanese, Marco; Gavazzo, Paola; Passalacqua, Mario; Nobile, Mario; Maura, Guido; Marcoli, Manuela
• Is Part Of: Journal of neurochemistry. Volume 124:Number 6(2013:Mar.)
• Page Start: 821
• Page End: 831
• Publication Date: 2013-02-03
• Subjects: Neurochemistry -- Periodicals; 616.8042
• DOI: 10.1111/jnc.12143
• Languages: English
• ISSNs: 0022-3042

Abstract

<abstract abstract-type="main" xml:lang="en" id="jnc12143-abs-0001"> <title>Abstract</title> <p>P2X7 receptors trigger Ca²⁺‐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 Mg²⁺, 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 Ca²⁺ elevation. No glutamate efflux was observed through the P2X2 receptor. Notably, HEK293 cells (lacking the machinery for Ca²⁺‐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.</p> </abstract>