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


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}

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

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