ArticleAmerican journal of respiratory and critical care medicine2016
AMP-activated Protein Kinase Deficiency Blocks the Hypoxic Ventilatory Response and Thus Precipitates Hypoventilation and Apnea.
Article in American journal of respiratory and critical care medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 52 citations in OpenAlex.
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- Effect of exercise on sleep and cardiopulmonary parameters in patients with pulmonary artery hypertension.Sleep & breathing = Schlaf & Atmung · 2021Trial
- Genetic adaptations shaping survival, pregnancy, and life at high altitude and sea level.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Review
- AdaptiveiScience · 2025Article
- Genetic map of the carotid body stem cell niche with focus on the OScientific reports · 2025Article
- Mapping Brain-Wide Neural Activity of Murine Attentional Processing in the Five-Choice Serial Reaction Time Task.Neuroscience bulletin · 2025Article
- AMPK Phosphorylates LMX1b to Regulate a Brainstem Neurogenic Network Important for Control of Breathing in Neonatal Mice.International journal of molecular sciences · 2024Article
- Pannonibacter tanglangensis sp. nov., a New Species Isolated from Pond Sediment.Journal of microbiology (Seoul, Korea) · 2024Article
- SubSol-HIe is an AMPK-dependent hypoxia-responsive subnucleus of the nucleus tractus solitarius that coordinates the hypoxic ventilatory response and protects against apnoea in mice.Pflugers Archiv : European journal of physiology · 2024Article
- Of Mice and Men and Plethysmography Systems: Does LKB1 Determine the Set Point of Carotid Body Chemosensitivity and the Hypoxic Ventilatory Response?Advances in experimental medicine and biology · 2023Article
- Chronic Metformin Administration Does Not Alter Carotid Sinus Nerve Activity in Control Rats.Advances in experimental medicine and biology · 2023Article
- AMPK facilitates the hypoxic ventilatory response through non-adrenergic mechanisms at the brainstem.Pflugers Archiv : European journal of physiology · 2023Article
- Constitutive Expression of Hif2α Confers Acute OAdvances in experimental medicine and biology · 2023Article
- Oxygen regulation of breathing is abolished in mitochondrial complex III-deficient arterial chemoreceptors.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- LKB1 is the gatekeeper of carotid body chemosensing and the hypoxic ventilatory response.Communications biology · 2022Article
- Effect of a Plateau Environment on the Oxidation State of the Heart and Liver through AMPK/p38 MAPK/Nrf2-ARE Signaling Pathways in Tibetan and DLY Pigs.Animals : an open access journal from MDPI · 2022Article
- Are Multiple Mitochondrial Related Signalling Pathways Involved in Carotid Body Oxygen Sensing?Frontiers in physiology · 2022Review
- Oxygen-dependent regulation of ion channels: acute responses, post-translational modification, and response to chronic hypoxia.Pflugers Archiv : European journal of physiology · 2021Review
- Carotid body chemoreceptors: physiology, pathology, and implications for health and disease.Physiological reviews · 2021Review
- AMPK and the Need to Breathe and Feed: What's the Matter with Oxygen?International journal of molecular sciences · 2020Review
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
rationaleModulation of breathing by hypoxia accommodates variations in oxygen demand and supply during, for example, sleep and ascent to altitude, but the precise molecular mechanisms of this phenomenon remain controversial. Among the genes influenced by natural selection in high-altitude populations is one for the adenosine monophosphate-activated protein kinase (AMPK) α1-catalytic subunit, which governs cell-autonomous adaptations during metabolic stress.
objectivesWe investigated whether AMPK-α1 and/or AMPK-α2 are required for the hypoxic ventilatory response and the mechanism of ventilatory dysfunctions arising from AMPK deficiency.
methodsWe used plethysmography, electrophysiology, functional magnetic resonance imaging, and immediate early gene (c-fos) expression to assess the hypoxic ventilatory response of mice with conditional deletion of the AMPK-α1 and/or AMPK-α2 genes in catecholaminergic cells, which compose the hypoxia-responsive respiratory network from carotid body to brainstem. MEASUREMENTS AND MAIN
resultsAMPK-α1 and AMPK-α2 deletion virtually abolished the hypoxic ventilatory response, and ventilatory depression during hypoxia was exacerbated under anesthesia. Rather than hyperventilating, mice lacking AMPK-α1 and AMPK-α2 exhibited hypoventilation and apnea during hypoxia, with the primary precipitant being loss of AMPK-α1 expression. However, the carotid bodies of AMPK-knockout mice remained exquisitely sensitive to hypoxia, contrary to the view that the hypoxic ventilatory response is determined solely by increased carotid body afferent input to the brainstem. Regardless, functional magnetic resonance imaging and c-fos expression revealed reduced activation by hypoxia of well-defined dorsal and ventral brainstem nuclei.
conclusionsAMPK is required to coordinate the activation by hypoxia of brainstem respiratory networks, and deficiencies in AMPK expression precipitate hypoventilation and apnea, even when carotid body afferent input is normal.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.