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. P2X(7) 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 alpha,beta-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 P2X(7) 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 P2X(7) knockouts. Hence, cortical astroglia of rats and mice possess functional P2X(7) receptors. These receptors may participate in necrotic/apoptotic or proliferative reactions after stimulation by large quantities of ATP released by central nervous system injury.