Rodent cortical astroglia express in situ functional P2X7 receptors sensing pathologically high ATP concentrations.
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.
Oliveira
João Filipe
JF
Rudolf-Boehm-Institute of Pharmacology and Toxicology, University of Leipzig, D-04107 Leipzig, Germany.
Riedel
Thomas
T
Leichsenring
Anna
A
Heine
Claudia
C
Franke
Heike
H
Krügel
Ute
U
Nörenberg
Wolfgang
W
Illes
Peter
P
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*
D058486:Receptors, Purinergic P2X7; D000255:Adenosine Triphosphate