Glial Intercellular Waves

Abstract

Glial cells have long been assigned a supporting role in the nervous system, in which they help maintain and modulate neuronal metabolism. However, recent attention has focused on the ability of astrocytes to propagate long-range calcium signals and actively communicate with each other, as well as with neurons and vascular cells. Synaptic activity in neurons triggers an increase in the intracellular calcium concentration ([Ca2+]i) of neighboring astrocytes, stimulating the release of ATP and glutamate. The released ATP stimulates an increase in [Ca2+]i in neighboring astrocytes so that a "calcium wave" is propagated from cell to cell. Released glutamate is cotransported with Na+ into neighboring cells; thus, glutamate uptake leads to an increase in astrocyte intracellular sodium concentration ([Na+]i) that is also propagated from cell to cell. This increase in [Na+]i stimulates an increase in glucose uptake and metabolism that leads to the formation of lactate, which is delivered to nearby--and perhaps distant--neurons as an energy substrate. Thus, long-range intercellular calcium signaling in astrocytes may enable them to spatially coordinate their function in supporting neuronal metabolism.