title: Rodent cortical astroglia express in situ functional P2X7 receptors sensing pathologically high ATP concentrations.
abstract: ATP is an important neuronal and astroglial signaling molecule in the brain. In the present study, brain slices were prepared from the prefrontal cortex (PFC) of Wistar rats and 2 lines of mice. P2X₇ receptor immunoreactivity was colocalized with astro- and microglial but not neuronal markers. Whole-cell patch-clamp recordings showed that, in astroglial cells, dibenzoyl-ATP (BzATP) and ATP caused inward currents, near the resting membrane potential. The inactivity of α,β-methylene ATP, as well as the potency increases of BzATP and ATP in a low divalent cation (X²(+))-containing superfusion medium suggested the involvement of P2X₇ receptors. This idea was corroborated by the inhibition of these current responses by PPADS, Brilliant Blue G, A 438079, and calmidazolium. Ivermectin, trinitrophenyl-adenosine-5'-triphosphate, and cyclopentyl-dipropylxanthine did not alter the agonist effects. The reversal potential of BzATP was near 0 mV, indicating the opening of cationic receptor channels. In a low X²(+) superfusion medium, ATP-induced current responses in PFC astroglial cells of wild-type mice but not of the P2X₇ knockouts. Hence, cortical astroglia of rats and mice possess functional P2X₇ receptors. These receptors may participate in necrotic/apoptotic or proliferative reactions after stimulation by large quantities of ATP released by central nervous system injury.
authors.affiliation: Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, D-04107 Leipzig, Germany.
authors.forename: João Filipe
authors.initials: JF
authors.lastname: Oliveira
authors.forename: Thomas
authors.initials: T
authors.lastname: Riedel
authors.forename: Anna
authors.initials: A
authors.lastname: Leichsenring
authors.forename: Claudia
authors.initials: C
authors.lastname: Heine
authors.forename: Heike
authors.initials: H
authors.lastname: Franke
authors.forename: Ute
authors.initials: U
authors.lastname: Krügel
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Nörenberg
authors.forename: Peter
authors.initials: P
authors.lastname: Illes
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001923:Brain Chemistry; D002540:Cerebral Cortex / Q000502:physiology*; D005455:Fluorescent Antibody Technique; D008564:Membrane Potentials / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D051381:Rats; D017208:Rats, Wistar; D058486:Receptors, Purinergic P2X7 / Q000378:metabolism*
chemical_list: D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate