Ionotropic NMDA and P2X1/5 receptors mediate synaptically induced Ca2+ signalling in cortical astrocytes

Local, global and propagating calcium (Ca2+) signals provide the substrate for glial excitability. Here we analyse Ca2+ permeability of NMDA and P2X1/5 receptors expressed in cortical astrocytes and provide evidence that activation of these receptors trigger astroglial Ca2+ signals when stimulated by either endogenous agonists or by synaptic release of neurotransmitters. The Ca2+ permeability of the ionotropic receptors was determined by reversal potential shift analysis; the permeability ratio PCa/PK was 3.1 for NMDA receptors and 2.2 for P2X1/5 receptors. Selective stimulation of ionotropic receptors (with NMDA and α,β-methyleneATP) in freshly isolated cortical astrocytes induced ion currents associated with transient increases in cytosolic Ca2+ concentration ([Ca2+]i). Stimulation of neuronal afferents in cortical slices triggered glial synaptic currents and [Ca2+]i responses, which were partially blocked by selective antagonists of NMDA (D-AP5 and UBP141) and P2X1/5 (NF449) receptors. We conclude that ionotropic receptors contribute to astroglial Ca2+ signalling and may provide a specific mechanism for fast neuronal–glial signalling at the synaptic level.