title: Naked mole rats exhibit metabolic but not ventilatory plasticity following chronic sustained hypoxia.
abstract: Naked mole rats are among the most hypoxia-tolerant mammals identified and live in chronic hypoxia throughout their lives. The physiological mechanisms underlying this tolerance, however, are poorly understood. Most vertebrates hyperventilate in acute hypoxia and exhibit an enhanced hyperventilation following acclimatization to chronic sustained hypoxia (CSH). Conversely, naked mole rats do not hyperventilate in acute hypoxia and their response to CSH has not been examined. In this study, we explored mechanisms of plasticity in the control of the hypoxic ventilatory response (HVR) and hypoxic metabolic response (HMR) of freely behaving naked mole rats following 8-10 days of chronic sustained normoxia (CSN) or CSH. Specifically, we investigated the role of the major inhibitory neurotransmitter γ-amino butyric acid (GABA) in mediating these responses. Our study yielded three important findings. First, naked mole rats did not exhibit ventilatory plasticity following CSH, which is unique among adult animals studied to date. Second, GABA receptor (GABAR) antagonism altered breathing patterns in CSN and CSH animals and modulated the acute HVR in CSN animals. Third, naked mole rats exhibited GABAR-dependent metabolic plasticity following long-term hypoxia, such that the basal metabolic rate was approximately 25% higher in normoxic CSH animals than CSN animals, and GABAR antagonists modulated this increase.
authors.affiliation: Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Danielle
authors.initials: D
authors.lastname: Chung
authors.affiliation: Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Yvonne A
authors.initials: YA
authors.lastname: Dzal
authors.affiliation: Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: Allison
authors.initials: A
authors.lastname: Seow
authors.affiliation: Department of Zoology, University of British Columbia, Vancouver, British Columbia, Canada.
authors.forename: William K
authors.initials: WK
authors.lastname: Milsom
authors.affiliation: Department of Biology, University of Ottawa, Ottawa, Ontario, Canada mpamenter@uottawa.ca.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Pamenter
mesh_terms: D000064:Acclimatization; D000693:Anaerobiosis; D000818:Animals; D001481:Basal Metabolism / Q000187:drug effects; D001640:Bicuculline / Q000494:pharmacology; D005260:Female; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D058788:GABA-B Receptor Antagonists / Q000494:pharmacology; D008297:Male; D019577:Mole Rats / Q000502:physiology*; D009025:Morpholines / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism*; D011897:Random Allocation; D009435:Synaptic Transmission / Q000187:drug effects
chemical_list: C095804:(+)-(S)-5,5-dimethylmorpholinyl-2-acetic acid; D058787:GABA-A Receptor Antagonists; D058788:GABA-B Receptor Antagonists; D009025:Morpholines; D010100:Oxygen; D001640:Bicuculline
keywords: hypoxic metabolic response; hypoxic ventilatory response; plethysmography; respirometry; ventilatory acclimatization to hypoxia