Glial cells participate in bidirectional interactions with neurons and help sculpt brain function. For instance, astrocytes clear extracellular glutamate released during synaptic activity and can themselves release glutamate in response to increases in intracellular calcium ([Ca2+]i). Astrocytes propagate long-distance waves of increased [Ca2+]i through mechanisms that involve ATP release, purinergic receptor stimulation, and mobilization of inositol 1,4,5-trisphosphate (IP3) from intracellular stores. However, the function of these waves is not clear. Bernardinelli et al. visualized changes in [Na+]i and [Ca2+]i in primary cultures of mouse cortical astrocytes and observed propagation of Na+ and Ca2+ waves after electrical or mechanical stimulation of a single cell. The kinetics of Na+ and Ca2+ waves were distinct: whereas propagation of both was blocked by a purinergic receptor antagonist or by a cell-permeant Ca2+ chelator, only the propagation of Na+ waves was substantially reduced by gap junction blockade. Glutamate is released during Ca2+ waves, and inhibition of the glutamate transporter inhibited Na+ wave propagation. Increased [Na+]i stimulates astrocyte metabolic activity; thus; glutamate released during the Ca2+ wave may elicit a secondary Na+-mediated metabolic wave, potentially providing products of glycolysis to distant neurons. -- EMA
Proc. Natl. Acad. Sci. U.S.A. 101, 14937 (2004).
