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Connexin26 mediates CO2-dependent regulation of breathing via glial cells of the medulla oblongata
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van de Wiel, Joseph, Meigh, Louise, Bhandare, Amol M., Cook, Jonathan P., Nijjar, Sarbjit, Huckstepp, Robert T. R. and Dale, Nicholas (2020) Connexin26 mediates CO2-dependent regulation of breathing via glial cells of the medulla oblongata. Communications Biology, 3 (1). 521. doi:10.1038/s42003-020-01248-x ISSN 2399-3642.
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WRAP-connexin26-mediates-CO2-dependent-regulation-breathing-glial-cells-medulla-oblongata-Dale-2020.pdf - Published Version - Requires a PDF viewer. Available under License Creative Commons Attribution 4.0. Download (2628Kb) | Preview |
Official URL: https://doi.org/10.1038/s42003-020-01248-x
Abstract
Breathing is highly sensitive to the PCO2 of arterial blood. Although CO2 is detected via the proxy of pH, CO2 acting directly via Cx26 may also contribute to the regulation of breathing. Here we exploit our knowledge of the structural motif of CO2-binding to Cx26 to devise a dominant negative subunit (Cx26DN) that removes the CO2-sensitivity from endogenously expressed wild type Cx26. Expression of Cx26DN in glial cells of a circumscribed region of the mouse medulla - the caudal parapyramidal area – reduced the adaptive change in tidal volume and minute ventilation by approximately 30% at 6% inspired CO2. As central chemosensors mediate about 70% of the total response to hypercapnia, CO2-sensing via Cx26 in the caudal parapyramidal area contributed about 45% of the centrally-mediated ventilatory response to CO2. Our data unequivocally link the direct sensing of CO2 to the chemosensory control of breathing and demonstrates that CO2-binding to Cx26 is a key transduction step in this fundamental process.
| Item Type: | Journal Article | ||||||||||||
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| Subjects: | Q Science > QP Physiology | ||||||||||||
| Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||||||
| Library of Congress Subject Headings (LCSH): | Respiration -- Regulation, Neuroglia, Medulla oblongata | ||||||||||||
| Journal or Publication Title: | Communications Biology | ||||||||||||
| Publisher: | Nature Publishing Group | ||||||||||||
| ISSN: | 2399-3642 | ||||||||||||
| Official Date: | 21 September 2020 | ||||||||||||
| Dates: |
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| Volume: | 3 | ||||||||||||
| Number: | 1 | ||||||||||||
| Article Number: | 521 | ||||||||||||
| DOI: | 10.1038/s42003-020-01248-x | ||||||||||||
| Status: | Peer Reviewed | ||||||||||||
| Publication Status: | Published | ||||||||||||
| Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||
| Date of first compliant deposit: | 5 October 2020 | ||||||||||||
| Date of first compliant Open Access: | 8 October 2020 | ||||||||||||
| RIOXX Funder/Project Grant: |
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