 |
Previous Article | Next Article 
The Journal of Neuroscience, January 15, 2001, 21(2):477-484
Cytosolic Calcium Oscillations in Astrocytes May Regulate
Exocytotic Release of Glutamate
Lucia
Pasti1,
Micaela
Zonta1,
Tullio
Pozzan1,
Stefano
Vicini2, and
Giorgio
Carmignoto1
1 Department of Experimental Biomedical Sciences and
Consiglio Nazionale delle Ricerche Center for the Study of
Biomembranes, University of Padova, 35121 Padova, Italy, and
2 Department of Physiology and Biophysics, Georgetown
University, Washington, DC 20007
To obtain insights into the spatiotemporal characteristics and
mechanism of Ca2+-dependent glutamate release from
astrocytes, we developed a new experimental approach using human
embryonic kidney (HEK) 293 cells transfected with the
NMDA receptor (NMDAR), which act as glutamate biosensors, plated
on cultured astrocytes. We here show that oscillations of intracellular
Ca2+ concentration
([Ca2+]i) in astrocytes trigger
synchronous and repetitive [Ca2+]i
elevations in sensor HEK cells, and that these elevations are sensitive
to NMDAR inhibition. By whole-cell patch-clamp recordings, we
demonstrate that the activation of NMDARs in HEK cells results in
inward currents that often have extremely fast kinetics, comparable with those of glutamate-mediated NMDAR currents in postsynaptic neurons. We also show that the release of glutamate from stimulated astrocytes is drastically reduced by agents that are known to reduce
neuronal exocytosis, i.e., tetanus toxin and bafilomycin A1. We conclude that
[Ca2+]i oscillations represent a
frequency-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 synaptobrevin and vacuolar H+
ATPase suggest that astrocytes are endowed with an exocytotic mechanism
of glutamate release that resembles that of neurons.
Key words:
glia; calcium oscillations; transmitter release; exocytosis; SNARE protein; green fluorescent protein
Copyright © 2001 Society for Neuroscience 0270-6474/01/212477-08$05.00/0
This article has been cited by other articles:

|
 |

|
 |
 
H.-T. Liu, T. Akita, T. Shimizu, R. Z. Sabirov, and Y. Okada
Bradykinin-induced astrocyte\#8211;neuron signalling: glutamate release is mediated by ROS-activated volume-sensitive outwardly rectifying anion channels
J. Physiol.,
May 15, 2009;
587(10):
2197 - 2209.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. Ramamoorthy and M. D. Whim
Trafficking and Fusion of Neuropeptide Y-Containing Dense-Core Granules in Astrocytes
J. Neurosci.,
December 17, 2008;
28(51):
13815 - 13827.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Marchaland, C. Cali, S. M. Voglmaier, H. Li, R. Regazzi, R. H. Edwards, and P. Bezzi
Fast Subplasma Membrane Ca2+ Transients Control Exo-Endocytosis of Synaptic-Like Microvesicles in Astrocytes
J. Neurosci.,
September 10, 2008;
28(37):
9122 - 9132.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Petravicz, T. A. Fiacco, and K. D. McCarthy
Loss of IP3 Receptor-Dependent Ca2+ Increases in Hippocampal Astrocytes Does Not Affect Baseline CA1 Pyramidal Neuron Synaptic Activity
J. Neurosci.,
May 7, 2008;
28(19):
4967 - 4973.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. A. Hires, Y. Zhu, and R. Y. Tsien
Optical measurement of synaptic glutamate spillover and reuptake by linker optimized glutamate-sensitive fluorescent reporters
PNAS,
March 18, 2008;
105(11):
4411 - 4416.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Pangrsic, M. Potokar, M. Stenovec, M. Kreft, E. Fabbretti, A. Nistri, E. Pryazhnikov, L. Khiroug, R. Giniatullin, and R. Zorec
Exocytotic Release of ATP from Cultured Astrocytes
J. Biol. Chem.,
September 28, 2007;
282(39):
28749 - 28758.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. J. Lee, G. Mannaioni, H. Yuan, D. H. Woo, M. B. Gingrich, and S. F. Traynelis
Astrocytic control of synaptic NMDA receptors
J. Physiol.,
June 15, 2007;
581(3):
1057 - 1081.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. N. Bowser and B. S. Khakh
Vesicular ATP Is the Predominant Cause of Intercellular Calcium Waves in Astrocytes
J. Gen. Physiol.,
June 1, 2007;
129(6):
485 - 491.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Chuquet, L. Hollender, and E. A. Nimchinsky
High-Resolution In Vivo Imaging of the Neurovascular Unit during Spreading Depression
J. Neurosci.,
April 11, 2007;
27(15):
4036 - 4044.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. N. Bowser and B. S. Khakh
Two forms of single-vesicle astrocyte exocytosis imaged with total internal reflection fluorescence microscopy
PNAS,
March 6, 2007;
104(10):
4212 - 4217.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. J. Sweger, K. B. Casper, K. Scearce-Levie, B. R. Conklin, and K. D. McCarthy
Development of Hydrocephalus in Mice Expressing the Gi-Coupled GPCR Ro1 RASSL Receptor in Astrocytes
J. Neurosci.,
February 28, 2007;
27(9):
2309 - 2317.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Domercq, L. Brambilla, E. Pilati, J. Marchaland, A. Volterra, and P. Bezzi
P2Y1 Receptor-evoked Glutamate Exocytosis from Astrocytes: CONTROL BY TUMOR NECROSIS FACTOR-{alpha} AND PROSTAGLANDINS
J. Biol. Chem.,
October 13, 2006;
281(41):
30684 - 30696.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X.-K. Chen, Y.-F. Xiong, and Z. Zhou
"Kiss-and-Run" Exocytosis in Astrocytes
Neuroscientist,
October 1, 2006;
12(5):
375 - 378.
[Abstract]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Fellin, M. Gomez-Gonzalo, S. Gobbo, G. Carmignoto, and P. G. Haydon
Astrocytic Glutamate Is Not Necessary for the Generation of Epileptiform Neuronal Activity in Hippocampal Slices
J. Neurosci.,
September 6, 2006;
26(36):
9312 - 9322.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
W. Zhou, L.-W. Fu, S. C. Tjen-A-Looi, Z.-l. Guo, and J. C. Longhurst
Role of glutamate in a visceral sympathoexcitatory reflex in rostral ventrolateral medulla of cats
Am J Physiol Heart Circ Physiol,
September 1, 2006;
291(3):
H1309 - H1318.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
P. G. Haydon and G. Carmignoto
Astrocyte control of synaptic transmission and neurovascular coupling.
Physiol Rev,
July 1, 2006;
86(3):
1009 - 1031.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. Serrano, N. Haddjeri, J.-C. Lacaille, and R. Robitaille
GABAergic network activation of glial cells underlies hippocampal heterosynaptic depression.
J. Neurosci.,
May 17, 2006;
26(20):
5370 - 5382.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
B. Haas, C. G. Schipke, O. Peters, G. Sohl, K. Willecke, and H. Kettenmann
Activity-dependent ATP-waves in the Mouse Neocortex are Independent from Astrocytic Calcium Waves
Cereb Cortex,
February 1, 2006;
16(2):
237 - 246.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Crippa, U. Schenk, M. Francolini, P. Rosa, C. Verderio, M. Zonta, T. Pozzan, M. Matteoli, and G. Carmignoto
Synaptobrevin2-expressing vesicles in rat astrocytes: insights into molecular characterization, dynamics and exocytosis
J. Physiol.,
February 1, 2006;
570(3):
567 - 582.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. Rossi, L. Brambilla, C. F. Valori, A. Crugnola, G. Giaccone, R. Capobianco, M. Mangieri, A. E. Kingston, A. Bloc, P. Bezzi, et al.
Defective Tumor Necrosis Factor-{alpha}-dependent Control of Astrocyte Glutamate Release in a Transgenic Mouse Model of Alzheimer Disease
J. Biol. Chem.,
December 23, 2005;
280(51):
42088 - 42096.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
O. Pascual, K. B. Casper, C. Kubera, J. Zhang, R. Revilla-Sanchez, J.-Y. Sul, H. Takano, S. J. Moss, K. McCarthy, and P. G. Haydon
Astrocytic Purinergic Signaling Coordinates Synaptic Networks
Science,
October 7, 2005;
310(5745):
113 - 116.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
X. Chen, L. Wang, Y. Zhou, L.-H. Zheng, and Z. Zhou
"Kiss-and-Run" Glutamate Secretion in Cultured and Freshly Isolated Rat Hippocampal Astrocytes
J. Neurosci.,
October 5, 2005;
25(40):
9236 - 9243.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J. Petit-Jacques, B. Volgyi, B. Rudy, and S. Bloomfield
Spontaneous Oscillatory Activity of Starburst Amacrine Cells in the Mouse Retina
J Neurophysiol,
September 1, 2005;
94(3):
1770 - 1780.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
C. Rose, W. Kresse, and H. Kettenmann
Acute Insult of Ammonia Leads to Calcium-dependent Glutamate Release from Cultured Astrocytes, an Effect of pH
J. Biol. Chem.,
June 3, 2005;
280(22):
20937 - 20944.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
J.-P. Mothet, L. Pollegioni, G. Ouanounou, M. Martineau, P. Fossier, and G. Baux
Glutamate receptor activation triggers a calcium-dependent and SNARE protein-dependent release of the gliotransmitter D-serine
PNAS,
April 12, 2005;
102(15):
5606 - 5611.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
G. Perea and A. Araque
Properties of Synaptically Evoked Astrocyte Calcium Signal Reveal Synaptic Information Processing by Astrocytes
J. Neurosci.,
March 2, 2005;
25(9):
2192 - 2203.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
R. E. Haskew-Layton, A. A. Mongin, and H. K. Kimelberg
Hydrogen Peroxide Potentiates Volume-sensitive Excitatory Amino Acid Release via a Mechanism Involving Ca2+/Calmodulin-dependent Protein Kinase II
J. Biol. Chem.,
February 4, 2005;
280(5):
3548 - 3554.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. A. Mongin and H. K. Kimelberg
ATP regulates anion channel-mediated organic osmolyte release from cultured rat astrocytes via multiple Ca2+-sensitive mechanisms
Am J Physiol Cell Physiol,
January 1, 2005;
288(1):
C204 - C213.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. N. Bowser and B. S. Khakh
ATP Excites Interneurons and Astrocytes to Increase Synaptic Inhibition in Neuronal Networks
J. Neurosci.,
September 29, 2004;
24(39):
8606 - 8620.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
T. Fellin and G. Carmignoto
Neurone-to-astrocyte signalling in the brain represents a distinct multifunctional unit
J. Physiol.,
August 15, 2004;
559(1):
3 - 15.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. C. Angulo, A. S. Kozlov, S. Charpak, and E. Audinat
Glutamate Released from Glial Cells Synchronizes Neuronal Activity in the Hippocampus
J. Neurosci.,
August 4, 2004;
24(31):
6920 - 6927.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Q. Zhang, M. Fukuda, E. Van Bockstaele, O. Pascual, and P. G. Haydon
Synaptotagmin IV regulates glial glutamate release
PNAS,
June 22, 2004;
101(25):
9441 - 9446.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Q. Zhang, T. Pangrsic, M. Kreft, M. Krzan, N. Li, J.-Y. Sul, M. Halassa, E. Van Bockstaele, R. Zorec, and P. G. Haydon
Fusion-related Release of Glutamate from Astrocytes
J. Biol. Chem.,
March 26, 2004;
279(13):
12724 - 12733.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
V. Montana, Y. Ni, V. Sunjara, X. Hua, and V. Parpura
Vesicular Glutamate Transporter-Dependent Glutamate Release from Astrocytes
J. Neurosci.,
March 17, 2004;
24(11):
2633 - 2642.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Q.-s. Liu, Q. Xu, G. Arcuino, J. Kang, and M. Nedergaard
From The Cover: Astrocyte-mediated activation of neuronal kainate receptors
PNAS,
March 2, 2004;
101(9):
3172 - 3177.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
K. J. Todd, C. A. B. Slatter, and D. W. Ali
Activation of Ionotropic Glutamate Receptors on Peripheral Axons of Primary Motoneurons Mediates Transmitter Release at the Zebrafish NMJ
J Neurophysiol,
February 1, 2004;
91(2):
828 - 840.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Zonta, A. Sebelin, S. Gobbo, T. Fellin, T. Pozzan, and G. Carmignoto
Glutamate-mediated cytosolic calcium oscillations regulate a pulsatile prostaglandin release from cultured rat astrocytes
J. Physiol.,
December 1, 2003;
553(2):
407 - 414.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Morita, C. Higuchi, T. Moto, N. Kozuka, J. Susuki, R. Itofusa, J. Yamashita, and Y. Kudo
Dual Regulation of Calcium Oscillation in Astrocytes by Growth Factors and Pro-Inflammatory Cytokines via the Mitogen-Activated Protein Kinase Cascade
J. Neurosci.,
November 26, 2003;
23(34):
10944 - 10952.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. R. Fam, C. J. Gallagher, L. V. Kalia, and M. W. Salter
Differential Frequency Dependence of P2Y1- and P2Y2- Mediated Ca 2+ Signaling in Astrocytes
J. Neurosci.,
June 1, 2003;
23(11):
4437 - 4444.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Grimaldi, M. Maratos, and A. Verma
Transient Receptor Potential Channel Activation Causes a Novel Form of [Ca 2+]i Oscillations and Is Not Involved in Capacitative Ca 2+ Entry in Glial Cells
J. Neurosci.,
June 1, 2003;
23(11):
4737 - 4745.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
E. HANSSON and L. RONNBACK
Glial neuronal signaling in the central nervous system
FASEB J,
March 1, 2003;
17(3):
341 - 348.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
M. Krzan, M. Stenovec, M. Kreft, T. Pangrsic, S. Grilc, P. G. Haydon, and R. Zorec
Calcium-Dependent Exocytosis of Atrial Natriuretic Peptide from Astrocytes
J. Neurosci.,
March 1, 2003;
23(5):
1580 - 1583.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
I. F. Smith, J. P. Boyle, L. D. Plant, H. A. Pearson, and C. Peers
Hypoxic Remodeling of Ca2+ Stores in Type I Cortical Astrocytes
J. Biol. Chem.,
February 7, 2003;
278(7):
4875 - 4881.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Coco, F. Calegari, E. Pravettoni, D. Pozzi, E. Taverna, P. Rosa, M. Matteoli, and C. Verderio
Storage and Release of ATP from Astrocytes in Culture
J. Biol. Chem.,
January 3, 2003;
278(2):
1354 - 1362.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
D. A. Baker, Z.-X. Xi, H. Shen, C. J. Swanson, and P. W. Kalivas
The Origin and Neuronal Function of In Vivo Nonsynaptic Glutamate
J. Neurosci.,
October 15, 2002;
22(20):
9134 - 9141.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
Y. Dalezios, R. Lujan, R. Shigemoto, J. D. B. Roberts, and P. Somogyi
Enrichment of mGluR7a in the Presynaptic Active Zones of GABAergic and Non-GABAergic Terminals on Interneurons in the Rat Somatosensory Cortex
Cereb Cortex,
September 1, 2002;
12(9):
961 - 974.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
A. A. Mongin and H. K. Kimelberg
ATP potently modulates anion channel-mediated excitatory amino acid release from cultured astrocytes
Am J Physiol Cell Physiol,
August 1, 2002;
283(2):
C569 - C578.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
H. Muyderman, M. Angehagen, M. Sandberg, U. Bjorklund, T. Olsson, E. Hansson, and M. Nilsson
alpha 1-Adrenergic Modulation of Metabotropic Glutamate Receptor-induced Calcium Oscillations and Glutamate Release in Astrocytes
J. Biol. Chem.,
November 30, 2001;
276(49):
46504 - 46514.
[Abstract]
[Full Text]
[PDF]
|
 |
|

|
 |

|
 |
 
S. Vesce, P. Bezzi, and A. Volterra
Synaptic Transmission with the Glia
Physiology,
August 1, 2001;
16(4):
178 - 184.
[Abstract]
[Full Text]
[PDF]
|
 |
|
|

|