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


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.


  1. Chen, C. C. et al. A P2X purinoceptor expressed by a subset of sensory neurons. Nature 377, 428–431 (1995)

    ADS  CAS  Article  Google Scholar 

  2. Lewis, C. et al. Coexpression of P2X2 and P2X3 receptor subunits can account for ATP-gated currents in sensory neurons. Nature 377, 432–435 (1995)

    ADS  CAS  Article  Google Scholar 

  3. Cook, S. P., Vulchanova, L., Hargreaves, K. M., Elde, R. & McCleskey, E. W. Distinct ATP receptors on pain-sensing and stretch-sensing neurons. Nature 387, 505–508 (1997)

    ADS  CAS  Article  Google Scholar 

  4. Cockayne, D. A. et al. Urinary bladder hyporeflexia and reduced pain-related behaviour in P2X3-deficient mice. Nature 407, 1011–1015 (2000)

    ADS  CAS  Article  Google Scholar 

  5. Cook, S. P. & McCleskey, E. W. Cell damage excites nociceptors through release of cytosolic ATP. Pain 95, 41–47 (2002)

    CAS  Article  Google Scholar 

  6. Vlaskovska, M. et al. P2X3 knock-out mice reveal a major sensory role for urothelially released ATP. J. Neurosci. 21, 5670–5677 (2001)

    CAS  Article  Google Scholar 

  7. Souslova, V. et al. Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors. Nature 407, 1015–1017 (2000)

    ADS  CAS  Article  Google Scholar 

  8. Rong, W. et al. Pivotal role of nucleotide P2X2 receptor subunit of the ATP-gated ion channel mediating ventilatory responses to hypoxia. J. Neurosci. 23, 11315–11321 (2003)

    CAS  Article  Google Scholar 

  9. Loeschcke, H. H. Central chemosensitivity and the reaction theory. J. Physiol. (Lond.) 32, 1–24 (1982)

    Article  Google Scholar 

  10. Feldman, J. L., Mitchell, G. S. & Nattie, E. E. Breathing: rhythmicity, plasticity, chemosensitivity. Annu. Rev. Neurosci. 26, 239–266 (2003)

    CAS  Article  Google Scholar 

  11. Mulkey, D. K. et al. Respiratory control by ventral surface chemoreceptor neurons in rats. Nature Neurosci. 7, 1360–1369 (2004)

    CAS  Article  Google Scholar 

  12. Llaudet, E., Botting, N. P., Crayston, J. A. & Dale, N. A three-enzyme microelectrode sensor for detecting purine release from central nervous system. Biosens. Bioelectron. 18, 43–52 (2003)

    CAS  Article  Google Scholar 

  13. Llaudet, E., Hatz, S., Droniou, M. & Dale, N. Microelectrode biosensor for real-time measurement of ATP in biological tissue. Anal. Chem. 77, 3267–3273 (2005)

    CAS  Article  Google Scholar 

  14. Richter, D. W. & Spyer, K. M. Studying rhythmogenesis of breathing: comparison of in vivo and in vitro models. Trends Neurosci. 24, 464–472 (2001)

    CAS  Article  Google Scholar 

  15. Kawai, A., Ballantyne, D., Muckenhoff, K. & Scheid, P. Chemosensitive medullary neurones in the brainstem-spinal cord preparation of the neonatal rat. J. Physiol. (Lond.) 492, 277–292 (1996)

    CAS  Article  Google Scholar 

  16. Gourine, A. V., Atkinson, L., Deuchars, J. & Spyer, K. M. Purinergic signalling in the medullary mechanisms of respiratory control in the rat: respiratory neurones express the P2X2 receptor subunit. J. Physiol. (Lond.) 552, 197–211 (2003)

    CAS  Article  Google Scholar 

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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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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).

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