Glutamate and ATP at the Interface of Metabolism and Signaling in the Brain

Shinghua Ding, Ding, Shinghua

Astrocytes have been found to play important roles in physiology being fundamental for ionic homeostasis and glutamate clearance from the synaptic cleft by their plasma membrane glutamate transporters. Astrocytes are electrically non-excitable, but they exhibit Ca(2+) signaling, which now has been demonstrated to serve as an indirect mediator of neuron-glia bidirectional interactions through gliotransmission via tripartite synapses and to modulate synaptic function and plasticity. Spontaneous astrocytic Ca(2+) signaling was observed in vivo. Intercellular Ca(2+) waves in astrocytes can be evoked by a variety of stimulations. Astrocytes are critically involved in many pathological conditions including ischemic stroke. For example, it is well known that astrocytes become reactive and form glial scar after stroke. In animal models of some brain disorders, astrocytes have been shown to exhibit enhanced Ca(2+) excitability featured as regenerative intercellular Ca(2+) waves. This chapter briefly summarizes astrocytic Ca(2+) signaling pathways under normal conditions and in experimental in vitro and in vivo ischemic models. It discusses the possible mechanisms and therapeutic implication underlying the enhanced astrocytic Ca(2+) excitability in stroke.