Changes in P2Y and P2X purinoceptors in reactive glia following axonal degeneration in the rat optic nerve

Abstract

Purinoceptors have been shown to be important in mediating Ca(2+) signalling in glial cells and it has been proposed that they may have a role in their response to injury. To investigate this, the glial response to adenosine 5'triphosphate (ATP) was measured in situ, in optic nerves from juvenile rats that were enucleated at postnatal day (P) 1; age-matched normal nerves were used as controls. The optic nerve is a typical central nervous system (CNS) white matter tract containing axons and glial cells, but not neurones or synapses. Following neonatal enucleation, axons degenerate and oligodendrocytes do not develop, so that the optic nerve is populated predominantly by reactive astrocytes, with a minor population of activated microglia. Application of 1 mM ATP evoked a large and rapid increase in glial [Ca(2+)](i) in fura-2 ratiometric whole nerve recordings from normal and gliotic axon-free nerves. Significantly, the response to ATP had a prolonged duration in gliotic axon-free nerves and there was as shift in the agonist rank order of potency from ATP = ADP > UTP >> alpha,beta-metATP to ATP > ADP = UTP = alpha,beta-metATP. The results indicate an in situ role for ATP signalling in reactive astrocytes, via metabotropic P2Y(1) and P2Y(2/4) purinoceptors and ionotropic P2X purinoreceptors. The change in the purinoceptor profile following axon degeneration suggests a special role for P2X purinoceptors in mediating the glial reaction to CNS injury.