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This Article Free via Open Access: OA OA Full Text Full Text (PDF) OA All Versions of this Article: 586/16/3963    most recent jphysiol.2008.154567v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Google Scholar Articles by Gourine, A. V. Articles by Spyer, K. M. PubMed PubMed Citation Articles by Gourine, A. V. Articles by Spyer, K. M. Related Collections Respiratory

¹ Department of Physiology, University College London, Gower Street, London WC1E 6BT, UK
² Department of Biological Sciences, University of Warwick, Coventry CV4 7AL, UK

The Breuer–Hering inflation reflex is initiated by activation of the slowly adapting pulmonary stretch receptor afferents (SARs), which monosynaptically activate second-order relay neurones in the dorsal medullary nucleus of the solitary tract (NTS). Here we demonstrate that during lung inflation SARs release both ATP and glutamate from their central terminals to activate these NTS neurones. In anaesthetized and artificially ventilated rats, ATP- and glutamate-selective microelectrode biosensors placed in the NTS detected rhythmic release of both transmitters phase-locked to lung inflation. This release of ATP and glutamate was independent of the centrally generated respiratory rhythm and could be reversibly abolished during the blockade of the afferent transmission in the vagus nerve by topical application of local anaesthetic. Microionophoretic application of ATP increased the activity of all tested NTS second-order relay neurones which receive monosynaptic inputs from the SARs. Unilateral microinjection of ATP into the NTS site where pulmonary stretch receptor afferents terminate produced central apnoea, mimicking the effect of lung inflation. Application of P2 and glutamate receptor antagonists (pyridoxal-5'-phosphate-6-azophenyl-2',4'-disulphonic acid, suramin and kynurenic acid) significantly decreased baseline lung inflation-induced firing of the second-order relay neurones. These data demonstrate that ATP and glutamate are released in the NTS from the central terminals of the lung stretch receptor afferents, activate the second-order relay neurones and hence mediate the key respiratory reflex – the Breuer–Hering inflation reflex.

(Received 27 March 2008; accepted after revision 26 June 2008; first published online 10 July 2008)
Corresponding author A. V. Gourine: Department of Physiology, University College London, Gower Street, London WC1E 6BT, UK.  Email: a.gourine{at}ucl.ac.uk

This article has been cited by other articles:

				V. A. Braga, D. B. Zoccal, and D. Accorsi-Mendonca Are ATP and glutamate released from slowly adapting pulmonary stretch receptor afferents in the NTS? J. Physiol., October 15, 2008; 586(20): 4791 - 4792. [Full Text] [PDF]