Cytosolic calcium oscillations in astrocytes may regulate exocytotic release of glutamate

Citation
L. Pasti et al., Cytosolic calcium oscillations in astrocytes may regulate exocytotic release of glutamate, J NEUROSC, 21(2), 2001, pp. 477-484
Citations number
45
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Neurosciences & Behavoir
Journal title
JOURNAL OF NEUROSCIENCE
ISSN journal
0270-6474 → ACNP
Volume
21
Issue
2
Year of publication
2001
Pages
477 - 484
Database
ISI
SICI code
0270-6474(20010115)21:2<477:CCOIAM>2.0.ZU;2-Y
Abstract
To obtain insights into the spatiotemporal characteristics and mechanism of Ca2+-dependent glutamate release from astrocytes, we developed a new exper imental approach using human embryonic kidney (HEK) 293 cells transfected w ith the NMDA receptor (NMDAR), which act as glutamate biosensors, plated on cultured astrocytes. We here show that oscillations of intracellular Ca2concentration ([Ca2+](i)) in astrocytes trigger synchronous and repetitive [Ca2+](i) elevations in sensor HEK cells, and that these elevations are sen sitive to NMDAR inhibition. By whole-cell patch-clamp recordings, we demons trate that the activation of NMDARs in HEK cells results in inward currents that often have extremely fast kinetics, comparable with those of glutamat e-mediated NMDAR currents in postsynaptic neurons. We also show that the re lease of glutamate from stimulated astrocytes is drastically reduced by age nts that are known to reduce neuronal exocytosis, i.e., tetanus toxin and b afilomycin A(1). We conclude that [Ca2+](i) oscillations represent a freque ncy-encoded signaling system that controls a pulsatile release of glutamate from astrocytes. The fast activation of NMDARs in the sensor cells and the dependence of glutamate release on the functional integrity of both synapt obrevin and vacuolar H+ ATPase suggest that astrocytes are endowed with an exocytotic mechanism of glutamate release that resembles that of neurons.