ATP is a mediator of chemosensory transduction in the central nervous system

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Abstract

Extracellular signalling by the purine nucleotide ATP has long been associated with sensory function1,2,3,4,5,6,7,8. In the periphery, ATP mediates nociception3,4,5, mechanosensitivity3,6, thermal sensitivity7 and O2 chemosensitivity8. These processes share a common mechanism that involves the release of ATP to excite afferent fibres via activation of ionotropic P2X and/or metabotropic P2Y receptors. Chemosensors located in the brainstem are crucial for the maintenance of physiological levels of blood gases through the regulation of breathing9,10,11. Here we show that an increase in pCO2 in the arterial blood triggers the immediate release of ATP from three chemosensitive regions located on the ventral surface of the medulla oblongata. Blockade of ATP receptors at these sites diminishes the chemosensory control of breathing, suggesting that ATP release constitutes a key step in central chemosensory transduction. These new data suggest that ATP, a phylogenetically ancient, unique and simple molecule, has been widely used in the evolution of afferent systems to mediate distinct forms of sensory transduction not only in the periphery but also within the central nervous system.

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Figure 1: Rapid CO 2 -induced release of ATP from the ventral surface of the medulla.
Figure 2: CO 2 induces ATP release from the classical chemosensitive areas of the ventral medullary surface.
Figure 3: ATP receptor blockade on the chemosensitive areas of the ventral medullary surface attenuates the effect of CO 2 on breathing in rats.
Figure 4: ATP applied to the chemosensitive areas of the ventral medullary surface mimics the effect of CO 2 on breathing in rats.

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Acknowledgements

We thank M. E. Droniou for help with the initial development of the ATP sensor. We also thank the Biotechnology and Biological Sciences Research Council (K.M.S., A.V.G.) and the Wellcome Trust (N.D.) for support.

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Correspondence to Alexander V. Gourine.

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Competing interests

N.D. and E.L. are founders of, and hold equity in, Sarissa Biomedical Ltd. Sarissa Biomedical Ltd. offers for sale ATP biosensors similar to some of those used in this article.

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Gourine, A., Llaudet, E., Dale, N. et al. ATP is a mediator of chemosensory transduction in the central nervous system. Nature 436, 108–111 (2005) doi:10.1038/nature03690

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