{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T19:56:10Z","timestamp":1787169370356,"version":"build-2736575974"},"reference-count":180,"publisher":"Portland Press Ltd.","issue":"17","license":[{"start":{"date-parts":[[2019,7,25]],"date-time":"2019-07-25T00:00:00Z","timestamp":1564012800000},"content-version":"vor","delay-in-days":1059,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2016,9,1]]},"abstract":"<jats:p>Regulation of breathing is critical to our capacity to accommodate deficits in oxygen availability and demand during, for example, sleep and ascent to altitude. It is generally accepted that a fall in arterial oxygen increases afferent discharge from the carotid bodies to the brainstem and thus delivers increased ventilatory drive, which restores oxygen supply and protects against hypoventilation and apnoea. However, the precise molecular mechanisms involved remain unclear. We recently identified as critical to this process the AMP-activated protein kinase (AMPK), which is key to the cell-autonomous regulation of metabolic homoeostasis. This observation is significant for many reasons, not least because recent studies suggest that the gene for the AMPK-\u03b11 catalytic subunit has been subjected to natural selection in high-altitude populations. It would appear, therefore, that evolutionary pressures have led to AMPK being utilized to regulate oxygen delivery and thus energy supply to the body in the short, medium and longer term. Contrary to current consensus, however, our findings suggest that AMPK regulates ventilation at the level of the caudal brainstem, even when afferent input responses from the carotid body are normal. We therefore hypothesize that AMPK integrates local hypoxic stress at defined loci within the brainstem respiratory network with an index of peripheral hypoxic status, namely afferent chemosensory inputs. Allied to this, AMPK is critical to the control of hypoxic pulmonary vasoconstriction and thus ventilation\u2013perfusion matching at the lungs and may also determine oxygen supply to the foetus by, for example, modulating utero-placental blood flow.<\/jats:p>","DOI":"10.1042\/bcj20160002","type":"journal-article","created":{"date-parts":[[2016,8,29]],"date-time":"2016-08-29T19:42:18Z","timestamp":1472499738000},"page":"2561-2572","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["The emerging role of AMPK in the regulation of breathing and oxygen supply"],"prefix":"10.1042","volume":"473","author":[{"given":"A.\u00a0Mark","family":"Evans","sequence":"first","affiliation":[{"name":"Centre for Integrative Physiology, College of Medicine and Veterinary Medicine, Hugh Robson Building, University of Edinburgh, Edinburgh EH8 9XD, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amira\u00a0D.","family":"Mahmoud","sequence":"additional","affiliation":[{"name":"Centre for Integrative Physiology, College of Medicine and Veterinary Medicine, Hugh Robson Building, University of Edinburgh, Edinburgh EH8 9XD, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Moral-Sanz","sequence":"additional","affiliation":[{"name":"Centre for Integrative Physiology, College of Medicine and Veterinary Medicine, Hugh Robson Building, University of Edinburgh, Edinburgh EH8 9XD, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandy","family":"Hartmann","sequence":"additional","affiliation":[{"name":"Centre for Integrative Physiology, College of Medicine and Veterinary Medicine, Hugh Robson Building, University of Edinburgh, Edinburgh EH8 9XD, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2016,8,30]]},"reference":[{"key":"2021112216302042800_B1","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1113\/jphysiol.2006.108381","article-title":"AMP-activated protein kinase and the regulation of Ca2+ signalling in O2-sensing cells","volume":"574","author":"Evans","year":"2006","journal-title":"J. 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