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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
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.
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).
Elizabeth M. Adler (9 November 2010) Sci. Signal.3 (147), eg11.
[DOI: 10.1126/scisignal.3147eg11] |Abstract »|Full Text »|PDF »
PODCASTS
R. Douglas Fields and Annalisa M. VanHook (9 November 2010) Sci. Signal.3 (147), pc20.
[DOI: 10.1126/scisignal.3147pc20] |Abstract »|Full Text »|Podcast »
PERSPECTIVES
Klaus Ballanyi, Bogdan Panaitescu, and Araya Ruangkittisakul (9 November 2010) Sci. Signal.3 (147), pe41.
[DOI: 10.1126/scisignal.3147pe41] |Abstract »|Full Text »|PDF »|Movies »
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.
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.
Present address: Department of Neurology, Children’s Hospital Boston, CLS 13060, 3 Blackfan Circle, Boston, MA 02115, USA.
