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 Ca
2+
waves. Here we show that intercellular Na
+
waves are also evoked by activation of single cultured cortical mouse astrocytes in parallel with Ca
2+
waves; however, there are spatial and temporal differences. Indeed, maneuvers that inhibit Ca
2+
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 Ca
2+
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.