V. Parpura et Pg. Haydon, Physiological astrocytic calcium levels stimulate glutamate release to modulate adjacent neurons, P NAS US, 97(15), 2000, pp. 8629-8634
Citations number
26
Categorie Soggetti
Multidisciplinary
Journal title
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
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.