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PNAS 101 (41): 14937-14942

Copyright © 2004 by the National Academy of Sciences.


Astrocytes generate Na+-mediated metabolic waves

Yann Bernardinelli *, Pierre J. Magistretti *, {dagger}, and Jean-Yves Chatton *, {ddagger}, §

*Department of Physiology, {dagger}Center for Psychiatric Neurosciences, and {ddagger}Cellular Imaging Facility, University of Lausanne, CH-1005 Lausanne, Switzerland

Edited by Harald Reuter, University of Bern, Bern, Switzerland, and approved September 8, 2004

Received for publication July 22, 2004.

Abstract: Glutamate-evoked Na+ increase in astrocytes has been identified as a signal coupling synaptic activity to glucose consumption. Astrocytes participate in multicellular signaling by transmitting intercellular Ca2+ waves. Here we show that intercellular Na+ waves are also evoked by activation of single cultured cortical mouse astrocytes in parallel with Ca2+ waves; however, there are spatial and temporal differences. Indeed, maneuvers that inhibit Ca2+ waves also inhibit Na+ waves; however, inhibition of the Na+/glutamate cotransporters or enzymatic degradation of extracellular glutamate selectively inhibit the Na+ wave. Thus, glutamate released by a Ca2+ wave-dependent mechanism is taken up by the Na+/glutamate cotransporters, resulting in a regenerative propagation of cytosolic Na+ increases. The Na+ wave gives rise to a spatially correlated increase in glucose uptake, which is prevented by glutamate transporter inhibition. Therefore, astrocytes appear to function as a network for concerted neurometabolic coupling through the generation of intercellular Na+ and metabolic waves.

Author contributions: Y.B., P.J.M., and J.-Y.C. designed research; Y.B. and J.-Y.C. performed research; Y.B. and J.-Y.C. analyzed data; and Y.B., P.J.M., and J.-Y.C. wrote the paper.

This paper was submitted directly (Track II) to the PNAS office.

Abbreviations: SBFI, sodium-binding benzofuran isophthalate; 2-NBD-glucose, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose; TBOA, threo-{beta}-benzyloxyaspartate; BAPTA, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate; , intracellular Na+; , intracellular Ca2+; AM, acetoxymethyl ester.

§ To whom correspondence should be addressed. E-mail: jean-yves.chatton{at}

© 2004 by The National Academy of Sciences of the USA

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