Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Subscribe

Logo for

PNAS 102 (45): 16466-16471

Copyright © 2005 by the National Academy of Sciences.

NEUROSCIENCE

Receptor-mediated glutamate release from volume sensitive channels in astrocytes

Takahiro Takano * {dagger}, Jian Kang {dagger}, {ddagger}, Jyoti K. Jaiswal §, Sanford M. Simon §, Jane H.-C. Lin ¶, Yufei Yu ¶, Yuxing Li ¶, Jay Yang ||, Gerald Dienel **, H. Ronald Zielke {dagger}{dagger}, and Maiken Nedergaard *, {ddagger}{ddagger}

*Center for Aging and Developmental Biology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642; Departments of {ddagger}Cell Biology and Pathology, New York Medical College, 30 Sunshine Cottage Road, Valhalla, NY 10595; §Laboratory of Cellular Biophysics, The Rockefeller University, 1230 York Avenue, New York, NY 10021; ||Department of Anesthesiology, Columbia University Physicians and Surgeons, New York, NY 10032; **Department of Neurology, University of Arkansas for Medical Sciences, Little Rock, AR 77205; and {dagger}{dagger}Department of Pediatrics, University of Maryland, 655 West Baltimore Street, Baltimore, MD 21201

Edited by Charles F. Stevens, The Salk Institute for Biological Studies, La Jolla, CA, and approved September 22, 2005

Received for publication July 26, 2005.

Abstract: Several lines of work have shown that astrocytes release glutamate in response to receptor activation, which results in a modulation of local synaptic activity. Astrocytic glutamate release is Ca2+-dependent and occurs in conjunction with exocytosis of glutamate containing vesicles. However, astrocytes contain a millimolar concentration of cytosolic glutamate and express channels permeable to small anions, such as glutamate. Here, we tested the idea that astrocytes respond to receptor stimulation by dynamic changes in cell volume, resulting in volume-sensitive channel activation, and efflux of cytosolic glutamate. Confocal imaging and whole-cell recordings demonstrated that astrocytes exhibited a transient Ca2+-dependent cell volume increase, which activated glutamate permeable channels. HPLC analysis revealed that glutamate was released in conjunction with other amino acid osmolytes. Our observations indicate that volume-sensitive channel may constitute a previously uncharacterized target for modulation of astrocyte-neuronal interactions.

Key Words: electrophysiology • exocytosis • neurotransmitters • osmolarity • synapses

Author contributions: T.T., J.K., J.K.J., S.M.S., J.H.-C.L., G.D., H.R.Z., and M.N. designed research; T.T., J.K., J.K.J., J.H.-C.L., Y.Y., and Y.L. performed research; J.Y., G.D., and H.R.Z. contributed new reagents/analytic tools; and M.N. wrote the paper.

Conflict of interest statement: No conflicts declared.

This paper was submitted directly (Track II) to the PNAS office.

Abbreviations: AM, acetoxymethyl ester; BAPTA, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetate; Cx, connexin; FFA, flufenamic acid; NPPB, 5-nitro-2-(3-phenylpropylamino)benzoic acid; TeNT, tetanus neurotoxin; VSC, volume-sensitive channel.

{dagger} T.T. and J.K. contributed equally to this work.

{ddagger}{ddagger} To whom correspondence should be addressed. E-mail: nedergaard{at}urmc.rochester.edu.

© 2005 by The National Academy of Sciences of the USA

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Lack of Evidence for Vesicular Glutamate Transporter Expression in Mouse Astrocytes.
D. Li, K. Herault, K. Silm, A. Evrard, S. Wojcik, M. Oheim, E. Herzog, and N. Ropert (2013)
J. Neurosci. 33, 4434-4455
   Abstract »    Full Text »    PDF »
Neuronal D-Serine and Glycine Release Via the Asc-1 Transporter Regulates NMDA Receptor-Dependent Synaptic Activity.
D. Rosenberg, S. Artoul, A. C. Segal, G. Kolodney, I. Radzishevsky, E. Dikopoltsev, V. N. Foltyn, R. Inoue, H. Mori, J.-M. Billard, et al. (2013)
J. Neurosci. 33, 3533-3544
   Abstract »    Full Text »    PDF »
Optogenetic activation of LiGluR-expressing astrocytes evokes anion channel-mediated glutamate release.
D. Li, K. Herault, E. Y. Isacoff, M. Oheim, and N. Ropert (2012)
J. Physiol. 590, 855-873
   Abstract »    Full Text »    PDF »
Activation of P2Y receptors causes strong and persistent shrinkage of C11-MDCK renal epithelial cells.
S. V. Koltsova, A. Platonova, G. V. Maksimov, A. A. Mongin, R. Grygorczyk, and S. N. Orlov (2011)
Am J Physiol Cell Physiol 301, C403-C412
   Abstract »    Full Text »    PDF »
Structural Remodeling of Fibrous Astrocytes after Axonal Injury.
D. Sun, M. Lye-Barthel, R. H. Masland, and T. C. Jakobs (2010)
J. Neurosci. 30, 14008-14019
   Abstract »    Full Text »    PDF »
Nonsynaptic Communication Through ATP Release from Volume-Activated Anion Channels in Axons.
R. D. Fields and Y. Ni (2010)
Science Signaling 3, ra73
   Abstract »    Full Text »    PDF »
Neuronal release of D-serine: a physiological pathway controlling extracellular D-serine concentration.
D. Rosenberg, E. Kartvelishvily, M. Shleper, C. M. C. Klinker, M. T. Bowser, and H. Wolosker (2010)
FASEB J 24, 2951-2961
   Abstract »    Full Text »    PDF »
Extracellular osmolarity modulates G protein-coupled receptor-dependent ATP release from 1321N1 astrocytoma cells.
A. E. Blum, B. Corbett Walsh, and G. R. Dubyak (2010)
Am J Physiol Cell Physiol 298, C386-C396
   Abstract »    Full Text »    PDF »
Basal Release of ATP: An Autocrine-Paracrine Mechanism for Cell Regulation.
R. Corriden and P. A. Insel (2010)
Science Signaling 3, re1
   Abstract »    Full Text »    PDF »
Bestrophin-1 Encodes for the Ca2+-Activated Anion Channel in Hippocampal Astrocytes.
H. Park, S.-J. Oh, K.-S. Han, D. H. Woo, H. Park, G. Mannaioni, S. F. Traynelis, and C. J. Lee (2009)
J. Neurosci. 29, 13063-13073
   Abstract »    Full Text »    PDF »
KV7/M Channels Mediate Osmotic Modulation of Intrinsic Neuronal Excitability.
A. Caspi, F. Benninger, and Y. Yaari (2009)
J. Neurosci. 29, 11098-11111
   Abstract »    Full Text »    PDF »
Bradykinin-induced astrocyte-neuron signalling: glutamate release is mediated by ROS-activated volume-sensitive outwardly rectifying anion channels.
H.-T. Liu, T. Akita, T. Shimizu, R. Z. Sabirov, and Y. Okada (2009)
J. Physiol. 587, 2197-2209
   Abstract »    Full Text »    PDF »
Lysosomes Are the Major Vesicular Compartment Undergoing Ca2+-Regulated Exocytosis from Cortical Astrocytes.
D. Li, N. Ropert, A. Koulakoff, C. Giaume, and M. Oheim (2008)
J. Neurosci. 28, 7648-7658
   Abstract »    Full Text »    PDF »
Resolving vesicle fusion from lysis to monitor calcium-triggered lysosomal exocytosis in astrocytes.
J. K. Jaiswal, M. Fix, T. Takano, M. Nedergaard, and S. M. Simon (2007)
PNAS 104, 14151-14156
   Abstract »    Full Text »    PDF »
Glutamate-induced Exocytosis of Glutamate from Astrocytes.
J. Xu, H. Peng, N. Kang, Z. Zhao, J. H-C. Lin, P. K. Stanton, and J. Kang (2007)
J. Biol. Chem. 282, 24185-24197
   Abstract »    Full Text »    PDF »
VRACs CARVe a Path for Novel Mechanisms of Communication in the CNS.
S. J. Mulligan and B. A. MacVicar (2006)
Sci. STKE 2006, pe42
   Abstract »    Full Text »    PDF »
P2Y1 Receptor-evoked Glutamate Exocytosis from Astrocytes: CONTROL BY TUMOR NECROSIS FACTOR-{alpha} AND PROSTAGLANDINS.
M. Domercq, L. Brambilla, E. Pilati, J. Marchaland, A. Volterra, and P. Bezzi (2006)
J. Biol. Chem. 281, 30684-30696
   Abstract »    Full Text »    PDF »
Astrocyte control of synaptic transmission and neurovascular coupling..
P. G. Haydon and G. Carmignoto (2006)
Physiol Rev 86, 1009-1031
   Abstract »    Full Text »    PDF »
Neuron-derived D-Serine Release Provides a Novel Means to Activate N-Methyl-D-aspartate Receptors.
E. Kartvelishvily, M. Shleper, L. Balan, E. Dumin, and H. Wolosker (2006)
J. Biol. Chem. 281, 14151-14162
   Abstract »    Full Text »    PDF »

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882