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. Therefore, we hypothesized that GABAergic and/or adenosinergic signalling contributes to the blunted HVR and robust HMR in Damaraland mole-rats. To test this hypothesis, we injected adult animals with saline alone (controls), or 100 mg/kg aminophylline or 1 mg/kg bicuculline, to block adenosine or GABAA receptors, respectively. We then used respirometry, plethysmography, and thermal RFID probes to non-invasively measure metabolic, ventilatory, and thermoregulatory responses, respectively, to acute hypoxia (1 h in 5 or 7% O2) in awake and freely behaving animals. We found that bicuculline had relatively minor effects on metabolism and thermoregulation but sensitized ventilation such that the HVR became manifest at 7 instead of 5% O2 and was greater in magnitude. Aminophylline increased metabolic rate, ventilation, and body temperature (Tb) in normoxia, and augmented the HMR and HVR. Taken together, these findings indicate that adenosine- and GABAergic signalling plays important roles in mediating the robust HMR and blunted HVR in Damaraland mole-rats.