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ATP receptor-mediated synaptic currents in the central nervous system

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Abstract

UNTIL now, the only well documented, fast excitatory neurotrans-mitter in the brain has been glutamate. Although there is evidence for adenosine 5′-triphosphate (ATP) acting as a transmitter in the peripheral nervous system1–4, suggestions for such a role in the central nervous system1,5–11 have so far not been supported by any direct evidence. Here we report the recording of evoked and miniature synaptic currents in the rat medial habenula. The fast rise time of the currents showed that they were mediated by a ligand-activated ion channel rather than a second messenger system, thus limiting the known transmitter candidates. Evidence was found for the presence on the cells of glutamate, γ-aminobutyric acid, acetylcholine and ATP receptors, but not for 5-hydroxytryptamine (5HT3) or glycine receptors. The evoked currents were unaffected by blockers of glutamate, γ-aminobutyric acid or acetylcholine receptors but were blocked by the ATP receptor-blocker, suramin and the desensitizing ATP receptor-agonist α,β-methylene-ATP. Our evidence identifies for the first time synaptic currents in the brain, mediated directly by ATP receptors.

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Author notes

  1. Frances A. Edwards

    Present address: Department of Pharmacology, University of Sydney, New South Wales, 2006, Australia

Authors and Affiliations

  1. Department of Pharmacology, University College London, Gower Street, London, WC1E 6BT, UK

    Frances A. Edwards, Alasdair J. Gibb & David Colquhoun

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  1. Frances A. Edwards
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  2. Alasdair J. Gibb
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  3. David Colquhoun
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Edwards, F., Gibb, A. & Colquhoun, D. ATP receptor-mediated synaptic currents in the central nervous system. Nature 359, 144–147 (1992). https://doi.org/10.1038/359144a0

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