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CO2-Induced ATP-Dependent Release of Acetylcholine on the Ventral Surface of the Medulla Oblongata

Huckstepp, RTR; Llaudet, E; Gourine, AV; (2016) CO2-Induced ATP-Dependent Release of Acetylcholine on the Ventral Surface of the Medulla Oblongata. PLoS ONE , 11 (12) , Article e0167861. 10.1371/journal.pone.0167861. Green open access

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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.

Type: Article
Title: CO2-Induced ATP-Dependent Release of Acetylcholine on the Ventral Surface of the Medulla Oblongata
Open access status: An open access version is available from UCL Discovery
DOI: 10.1371/journal.pone.0167861
Publisher version: http://dx.doi.org/10.1371/journal.pone.0167861
Language: English
Additional information: © 2016 Huckste pp et al. This is an open access article distributed under the terms of the Creative Commons Attribution License , which permits unrestricte d use, distribu tion, and reproduction in any medium, provided the original author and source are credited.
Keywords: Science & Technology, Multidisciplinary Sciences, Carotid-Body Chemoreceptors, Central Co2 Chemoreception, Central-Nervous-System, Retrotrapezoid Nucleus, Brain-Stem, Ventilatory Response, Cholinergic Systems, Mammalian Brain, Astrocytes, Neurons
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Neuro, Physiology and Pharmacology
URI: http://discovery.ucl.ac.uk/id/eprint/1533193
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