Adenosine and γ-aminobutyric acid partially regulate metabolic and ventilatory responses of Damaraland mole-rats to acute hypoxia.

Fossorial Damaraland mole-rats (Fukomys damarensis) mount a robust hypoxic metabolic response (HMR) but a blunted hypoxic ventilatory response (HVR) to acute hypoxia. Although these reflex physiological responses have been described previously, the underlying signalling pathways are entirely unknown. Of particular interest are contributions from γ-aminobutyric acid (GABA), which is the primary inhibitory neurotransmitter in the nervous system of most adult mammals, and adenosine, the accumulation of which increases during hypoxia as a breakdown product of ATP.

The glutamatergic drive to breathe is reduced in severe but not moderate hypoxia in Damaraland mole-rats.

Damaraland mole-rats (Fukomys damarensis) are a hypoxia-tolerant fossorial species that exhibit a robust hypoxic metabolic response (HMR) and blunted hypoxic ventilatory response (HVR). Whereas the HVR of most adult mammals is mediated by increased excitatory glutamatergic signalling, naked mole-rats, which are closely related to Damaraland mole-rats, do not utilize this pathway. Given their phylogenetic relationship and similar lifestyles, we hypothesized that the signalling mechanisms underlying physiological responses to acute hypoxia in Damaraland mole-rats are like those of naked mole-rats.

Physiological responses to hypoxia are constrained by environmental temperature in heterothermic tenrecs.

Malagasy tenrecs are placental hibernating mammals that seal the entrances to their burrows and hibernate either singly or in groups for 8-9 months, which is likely to create a hypoxic and hypercapnic burrow environment. Therefore, we hypothesized that tenrecs are tolerant to environmental hypoxia and hypercapnia. Many hypoxia- and hypercapnia-tolerant fossorial mammals respond to hypoxia by decreasing metabolic rate and thermogenesis, and have blunted ventilatory responses to both environmental hypoxia and hypercapnia.

Burrowing star-nosed moles (Condylura cristata) are not hypoxia tolerant.

Star-nosed moles (Condylura cristata) have an impressive diving performance and burrowing lifestyle, yet no ventilatory data are available for this or any other talpid mole species. We predicted that, like many other semi-aquatic and fossorial small mammals, star-nosed moles would exhibit: (i) a blunted (i.e.

Na/K-ATPase activity is regionally regulated by acute hypoxia in naked mole-rat brain.

Matching ATP supply and demand is key to neuronal hypoxia-tolerance and failure to achieve this balance leads to excitotoxic cell death in most adult mammalian brains. Ion pumping is the most energy-demanding process in the brain and some hypoxia-tolerant vertebrates coordinately down-regulate ion movement across neuronal membranes to reduce the workload of energy-expensive ion pumps, and particularly the Na/K-ATPase. Naked mole-rats are among the most hypoxia-tolerant mammals and achieve a hypometabolic state while maintaining brain [ATP] during severe hypoxia; however, whether ionic homeostasis is plastic in naked mole-rat brain is unknown.

Naked mole-rats suppress energy metabolism and modulate membrane cholesterol in chronic hypoxia.

Naked mole-rats (NMRs) are mammalian champions of hypoxia tolerance that enter metabolic suppression to survive in low oxygen environments. Common physiological mechanisms used by animals to suppress metabolic rate include downregulating energy metabolism (ATP supply) as well as ion pumps (primary cellular ATP consumers). A recent goldfish study demonstrated that remodeling of membrane lipids may mediate these responses, but it is unknown if NMR employs the same strategies; therefore, we aimed to test the hypotheses that these fossorial mammals ) downregulate the activity of key enzymes of glycolysis, tricarboxylic acid (TCA) cycle, and β-oxidation, ) inhibit sodium-potassium-ATPase, and ) alter membrane lipids in response to chronic hypoxia.

Fossorial giant Zambian mole-rats have blunted ventilatory responses to environmental hypoxia and hypercapnia.

Fossorial giant Zambian mole-rats are believed to live in a hypoxic and hypercapnic subterranean environment but their physiological responses to these challenges are entirely unknown. To investigate this, we exposed awake and freely-behaving animals to i) 6 h of normoxia, ii) acute graded normocapnic hypoxia (21, 18, 15, 12, 8, and 5% O, 0% CO, balance N; 1 h each), or iii) acute graded normoxic hypercapnia (0, 2, 5, 7, 9, and 10% CO, 21% O, balance N; 1 h each), followed by a 1 h normoxic normocapnic recovery period, while non-invasively measuring ventilation, metabolic rate, and body temperature (T). We found that these mole-rats had a blunted hypoxic ventilatory response that manifested at 12% inhaled O, a robust hypoxic metabolic response (up to a 68% decrease, starting at 15% O), and decreased T (at or below 8% O).

Neurokinin-1 receptor activation is sufficient to restore the hypercapnic ventilatory response in the Substance P-deficient naked mole-rat.

Naked mole-rats (NMRs) live in large colonies within densely populated underground burrows. Their collective respiration generates significant metabolic carbon dioxide (CO) that diffuses slowly out of the burrow network, creating a hypercapnic environment. Currently, the physiological mechanisms that underlie the ability of NMRs to tolerate environmental hypercapnia are largely unknown.