Astrocytes generate Na+-mediated metabolic waves.
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.
Department of Physiology, University of Lausanne, CH-1005 Lausanne, Switzerland.
Yann
Y
Bernardinelli
Pierre J
PJ
Magistretti
Jean-Yves
JY
Chatton
D009327:4-Chloro-7-nitrobenzofurazan / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000502:physiology*; D001692:Biological Transport; D020013:Calcium Signaling / Q000502:physiology*; D002540:Cerebral Cortex / Q000502:physiology; D003847:Deoxyglucose / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D004558:Electric Stimulation; D007700:Kinetics; D051379:Mice; D008959:Models, Neurological; D010812:Physical Stimulation; D012964:Sodium / Q000502:physiology*; D009435:Synaptic Transmission / Q000502:physiology*
D003847:Deoxyglucose; D012964:Sodium; D009327:4-Chloro-7-nitrobenzofurazan; C098340:2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose