Waving to Far-Off Neurons?

Abstract

Far from the passive cellular "glue" implied by their name, 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 ([Ca 2+ ] i ). Astrocytes propagate long-distance waves of increased [Ca 2+ ] i through mechanisms that involve ATP release, purinergic receptor stimulation, and mobilization of inositol 1,4,5-trisphosphate (IP 3 ) from intracellular stores. However, the function of these waves is not clear. Bernardinelli et al. used fluorescent indicators to visualize changes in [Na + ] i and [Ca 2+ ] i in primary cultures of mouse cortical astrocytes and observed propagation of Na + and Ca 2+ waves after electrical or mechanical stimulation of a single cell. The kinetics of Na + and Ca 2+ waves were different and, whereas propagation of both was blocked by a purinergic receptor antagonist or by a cell-permeant Ca 2+ chelator, only the propagation of Na + waves was substantially reduced by gap junction blockade. Glutamate, whose uptake into astrocytes involves cotransport with Na + , is released during Ca 2+ waves, and glutamate transporter inhibition or extracellular exposure to glutamate oxidase or glutamate decarboxylase also inhibited the speed of Na + wave propagation without affecting propagation of Ca 2+ waves. Increased [Na + ] i stimulates astrocyte metabolic activity, and uptake of a fluorescent glucose analog was spatially correlated with and dependent on Na + waves. Thus, the authors propose that glutamate released during the Ca 2+ wave elicits a secondary Na + -mediated metabolic wave, which they suggest may be used to provide products of glycolysis to neurons remote from the initial site of stimulation. Y. Bernardinelli, P. J. Magistretti, J.-Y. Chatton, Astrocytes generate Na + -mediated metabolic waves. Proc. Natl. Acad. Sci. U.S.A. 101 , 14937-14942 (2004). [Abstract] [Full Text]