The carotid body (CB) is a sensor of systemic hypoxia, hypercapnia, acidosis and inflammation (Kumar & Bin-Jaliah, 2007). More recently, Gibbons et al (2022) have suggested a role for the CB in thermally-mediated hyperventilation in humans, although previous direct recordings of CB activity with changes in temperature remain equivocal (Alcayaga et al., 1993; Eyzaguirre et al., 1983; McQueen & Eyzaguirre, 1974). Furthermore, the exact mechanism of temperature sensing in the CB remains elusive.

All experiments and procedures were performed in accordance with the UK Animals (Scientific Procedures) Act 1986. Chemoafferent activity was measured in vitro from CBs dissected from adult male Wistar rats (200-300g). CB tissue was surgically removed under non-recovery anaesthesia (isoflurane (3-5%) in O₂ at a flow rate of 1.5L min^-1), death via cervical dislocation. CB preparations were superfused with a physiological salt solution equilibrated at 37°C and at a normocapnic, normoxic PO₂ to establish a baseline discharge between 0.25-1.5Hz. The CB was then cooled to 32°C, followed by steady incremental warming to 40°C over approximately 5 minutes (n=24 spikes, 10 animals). This protocol was repeated in hyperoxia (n=6 spikes, 6 animals), mild hypoxia in normocapnia (n=8 spikes, 7 animals) and during the addition of 100 µM 2-APB, a non-selective modulator of TRP channels, in normoxic normocapnia (n=8 spikes, 5 animals). Discharge was recorded at 1°C increments between 32°C and 40°C, results expressed as mean ±SEM and significance (P<0.05) was established by linear regression analysis.

Cooling the superfusate temperature from 37°C to 32°C in normoxia caused a rapid (within seconds) decrease in CB chemoafferent activity (0.84±0.11Hz vs 0.21±0.06Hz) which then increased linearly and significantly to 1.40±0.22Hz at 40°C (mean slope 0.130 Hz.^oC^-1; r² 0.925; P<0.001). This thermal effect was abolished by hyperoxia (mean slope 0.003 Hz.^oC^-1; r² 0.098; P>0.40). In mild hypoxia, decreasing the temperature from 37°C to 32°C still led to a rapid attenuation in chemoafferent activity (4.75±0.72Hz vs 0.47±0.12Hz) and subsequent increasing of temperature induced a linear increase in thermal response to 37°C (mean slope 0.766 Hz.^oC^-1; r² 0.972; P<0.001), the slope of which was increased 2.3 fold between 37°C to 40°C with a discharge of 9.74±1.19Hz at 40°C (mean slope 1.739 Hz.^oC^-1; r² 0.994). 2-APB greatly blunted the temperature sensing observed in mild hypoxia (mean slope between 32-40^oC, 0.109 Hz.^oC^-1; r² 0.801; P<0.05).

Overall, this data demonstrates that acute temperature sensing in the CB is PO₂ dependent, being abolished by hyperoxia and augmented by mild hypoxia. Thermal sensitivity during mild hypoxia is exaggerated above, rather than below, 37^oC, supporting the notion of a primary role for the CB in heat-induced hyperventilation (Gibbons et al., 2022). The augmented response to temperature in mild hypoxia may be regulated by TRP channels but future studies warrant the use of more selective drugs to determine the exact mechanism of acute temperature sensing in the CB.