Synchronization of Ca2+oscillations: involvement of ATP release in astrocytes

Glial cells, especially astrocytes, are not merely supportive cells, but are important partners to neighboring cells, including neurons, vascular cells, and other glial cells. Although glial cells are not excitable in terms of electrophysiology, they have been shown to generate synchronized Ca2+ transients (Ca2+ oscillations) through mechanisms of chemical coupling. Until recently, Ca2+ transients in astrocytes were thought to be totally dependent on neuronal activities, because astrocytes express a large variety of receptors for neurotransmitters and surround almost all synapses at which neurotransmitters are spilled over to stimulate astrocytes. In addition, however, astrocytes have been shown to release diffusible substances, so-called 'gliotransmitters', and Ca2+ transients in astrocytes are therefore also triggered by astrocytic activities, leading to propagation of Ca2+ transients or Ca2+ waves. In these processes, the gliotransmitter ATP and activation of P2Y receptors play central roles. Interestingly, astrocytes evoke Ca2+ transients when neurons are not present, suggesting that astrocytes themselves can initiate and control Ca2+ transients. Astrocytic Ca2+ transients are observed even in vivo, through mechanisms of chemical coupling by gliotransmitters, but they are less frequent and synchronous than those in vitro. Although we have not yet clarified their significance in the central nervous system, astrocytic Ca2+ transients are dramatically affected by pathological conditions, suggesting that, in addition to physiological events, they might be closely involved in disorders in the central nervous system.