Ca²⁺-dependent modulation of GABA_A and NMDA receptors by extracellular ATP: implication for function of tripartite synapse

The importance of communication between neuronal and glial cells for brain function is recognized by a modern concept of ‘tripartite synapse’. Astrocytes enwrap synapses and can modulate their activity by releasing gliotransmitters such as ATP, glutamate and D-serine. One of the regulatory pathways in the tripartite synapse is mediated by P2X purinoreceptors. Release of ATP from synaptic terminals and astrocytes activates Ca²⁺ influx via P2X purinoreceptors which co-localize with NMDA (N-methyl-D-aspartate) and GABA (γ-aminobutyric acid) receptors and can modulate their activity via intracellular cascades which involve phosphatase II and PKA (protein kinase A).