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

Sci. Signal., 5 October 2010
Vol. 3, Issue 142, p. ra73
[DOI: 10.1126/scisignal.2001128]

RESEARCH ARTICLES

Nonsynaptic Communication Through ATP Release from Volume-Activated Anion Channels in Axons

R. Douglas Fields* and Yingchun Ni{dagger}

Nervous Systems Development and Plasticity Section, National Institute of Child Health and Human Development, National Institutes of Health, Building 35, Room 2A211, MSC 3713, 35 Lincoln Drive, Bethesda, MD 20892, USA.

{dagger} Present address: Department of Neurology, Children’s Hospital Boston, CLS 13060, 3 Blackfan Circle, Boston, MA 02115, USA.

Abstract: The release of neuronal messengers outside synapses has broad biological implications, particularly with regard to communication between axons and glia. We identify a mechanism for nonsynaptic, nonvesicular release of adenosine triphosphate (ATP) from axons through volume-activated anion channels (VAACs) activated by microscopic axon swelling during action potential firing. We used a combination of single-photon imaging of ATP release, together with imaging for intrinsic optical signals, intracellular calcium ions (Ca2+), time-lapse video, and confocal microscopy, to investigate action potential–induced nonsynaptic release of this neurotransmitter. ATP release from cultured embryonic dorsal root ganglion axons persisted when bafilomycin or botulinum toxin was used to block vesicular release, whereas pharmacological inhibition of VAACs or prevention of action potential–induced axon swelling inhibited ATP release and disrupted activity-dependent signaling between axons and astrocytes. This nonvesicular, nonsynaptic communication could mediate various activity-dependent interactions between axons and nervous system cells in normal conditions, development, and disease.

* To whom correspondence should be addressed. E-mail: fieldsd{at}mail.nih.gov

Citation: R. D. Fields, Y. Ni, Nonsynaptic Communication Through ATP Release from Volume-Activated Anion Channels in Axons. Sci. Signal. 3, ra73 (2010).

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Mechanisms of heterosynaptic metaplasticity.
S. R. Hulme, O. D. Jones, C. R. Raymond, P. Sah, and W. C. Abraham (2013)
Phil Trans R Soc B 369, 20130148
   Abstract »    Full Text »    PDF »
Neurons respond directly to mechanical deformation with pannexin-mediated ATP release and autostimulation of P2X7 receptors.
J. Xia, J. C. Lim, W. Lu, J. M. Beckel, E. J. Macarak, A. M. Laties, and C. H. Mitchell (2012)
J. Physiol. 590, 2285-2304
   Abstract »    Full Text »    PDF »
Functional and Anatomical Identification of a Vesicular Transporter Mediating Neuronal ATP Release.
M. Larsson, K. Sawada, C. Morland, M. Hiasa, L. Ormel, Y. Moriyama, and V. Gundersen (2012)
Cereb Cortex 22, 1203-1214
   Abstract »    Full Text »    PDF »
Deletion of Ecto-5'-Nucleotidase (CD73) Reveals Direct Action Potential-Dependent Adenosine Release.
B. P. Klyuch, N. Dale, and M. J. Wall (2012)
J. Neurosci. 32, 3842-3847
   Abstract »    Full Text »    PDF »
Engrailed homeoprotein recruits the adenosine A1 receptor to potentiate ephrin A5 function in retinal growth cones.
O. Stettler, R. L. Joshi, A. Wizenmann, J. Reingruber, D. Holcman, C. Bouillot, F. Castagner, A. Prochiantz, and K. L. Moya (2012)
Development 139, 215-224
   Abstract »    Full Text »    PDF »
Control of Local Protein Synthesis and Initial Events in Myelination by Action Potentials.
H. Wake, P. R. Lee, and R. D. Fields (2011)
Science 333, 1647-1651
   Abstract »    Full Text »    PDF »
Axon Physiology.
D. Debanne, E. Campanac, A. Bialowas, E. Carlier, and G. Alcaraz (2011)
Physiol Rev 91, 555-602
   Abstract »    Full Text »    PDF »
Imaging Learning: The Search for a Memory Trace.
R. D. Fields (2011)
Neuroscientist 17, 185-196
   Abstract »    PDF »
Signaling by Neuronal Swelling.
R. D. Fields (2011)
Science Signaling 4, tr1
   Abstract »    Full Text »    PDF »
Visualizing Calcium Signaling in Astrocytes.
R. D. Fields (2010)
Science Signaling 3, tr5
   Abstract »    Full Text »    PDF »
Science Signaling Podcast: 9 November 2010.
R. D. Fields and A. M. VanHook (2010)
Science Signaling 3, pc20
   Abstract »    Full Text »
Change in the Brain's White Matter.
R. D. Fields (2010)
Science 330, 768-769
   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