Huckstepp, Robert T. R., Llaudet, Enrique and Gourine, Alexander V. (2016) CO2-induced ATP-dependent release of acetylcholine on the ventral surface of the medulla oblongata. PLoS One, 11 (12). e0167861. doi:10.1371/journal.pone.0167861

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Abstract

Complex mechanisms that detect changes in brainstem parenchymal PCO2/[H+] and trigger adaptive changes in lung ventilation are responsible for central respiratory CO2 chemosensitivity. Previous studies of chemosensory signalling pathways suggest that at the level of the ventral surface of the medulla oblongata (VMS), CO2-induced changes in ventilation are (at least in part) mediated by the release and actions of ATP and/or acetylcholine (ACh). Here we performed simultaneous real-time biosensor recordings of CO2-induced ATP and ACh release from the VMS in vivo and in vitro, to test the hypothesis that central respiratory CO2 chemosensory transduction involves simultaneous recruitment of purinergic and cholinergic signalling pathways. In anaesthetised and artificially ventilated rats, an increase in inspired CO2 triggered ACh release on the VMS with a peak amplitude of ~5 μM. Release of ACh was only detected after the onset of CO2-induced activation of the respiratory activity and was markedly reduced (by ~70%) by ATP receptor blockade. In horizontal slices of the VMS, CO2-induced release of ATP was reliably detected, whereas CO2 or bath application of ATP (100 μM) failed to trigger release of ACh. These results suggest that during hypercapnia locally produced ATP induces or potentiates the release of ACh (likely from the medullary projections of distal groups of cholinergic neurones), which may also contribute to the development and/or maintenance of the ventilatory response to CO2.

Item Type:	Journal Article
Subjects:	Q Science > QP Physiology
Divisions:	Faculty of Science > Life Sciences (2010- )
Library of Congress Subject Headings (LCSH):	Brain stem, Medulla oblongata, Lungs , Respiratory organs
Journal or Publication Title:	PLoS One
Publisher:	Public Library of Science
ISSN:	1932-6203
Official Date:	9 December 2016
Dates:	Date Event 9 December 2016 Published 21 November 2016 Accepted 5 September 2016 Submitted
Date of first compliant deposit:	12 December 2016
Volume:	11
Number:	12
Article Number:	e0167861
DOI:	10.1371/journal.pone.0167861
Status:	Peer Reviewed
Publication Status:	Published
Access rights to Published version:	Open Access
Funder:	Wellcome Trust (London, England)
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