Physiological astrocytic calcium levels stimulate glutamate release to modulate adjacent neurons

Astrocytes can release glutamate in a calcium-dependent manner and conseque ntly signal to adjacent neurons. Whether this glutamate release pathway is used during physiological signaling or is recruited only under pathophysiol ogical conditions is not well defined. One reason for this lack of understa nding is the limited knowledge about the levels of calcium necessary to sti mulate glutamate release from astrocytes and about how they compare with th e range of physiological calcium levels in these cells. We used flash photo lysis to raise internal calcium in astrocytes, while monitoring astrocytic calcium levels and glutamate, which evoked slow inward currents that were r ecorded electrophysiologically from single neurons grown on microislands of astrocytes. With this approach, we demonstrate that modest changes of astr ocytic calcium, from 84 to 140 nM, evoke substantial glutamatergic currents in neighboring neurons (-391 pA), with a Hill coefficient of 2.1 to 2.7. B ecause the agonists glutamate, norepinephrine. and dopamine all raise calci um in astrocytes to levels exceeding 1.8 mu M, these quantitative studies d emonstrate that the astrocytic glutamate release pathway is engaged at phys iological levels of internal calcium. Consequently, the calcium-dependent r elease of glutamate from astrocytes functions within an appropriate range o f astrocytic calcium levels to be used as a signaling pathway within the fu nctional nervous system.