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The hypoxic ventilatory response and TRPA1 antagonism in conscious mice
1Clinical Research Centre, National Hospital Organization Murayama Medical Center, Musashimurayama City, Japan; Medical Research Center, Polish Academy of Sciences, Warsaw, Poland.
Aim:
Recently, TRPA1 channels, richly expressed in both peripheral and central neural systems, have been proposed as novel sensors of changes in oxygen concentration along the hypoxic-hyperoxic continuum. In this study, we investigated the hypothesis that TRPA1 channels blockade should profoundly affect the hypoxic ventilatory response (HVR).
Methods:
We examined the chemosensory ventilatory responses in conscious mice before and after intraperitoneal administration of the specific TRPA1 antagonist HC-030031 in two doses of 50 and 200 (cumulative dose 250) mg kg(-1) . Ventilation and its responses to mild 13% and severe 7% hypoxia, pure O2 , and 5% CO2 in O2 were recorded in a whole-body plethysmograph.
Results:
TRPA1 antagonism caused a dose-dependent attenuation of the HVR. Ventilatory stimulation was virtually abrogated in response to the mild, but it remained viable, albeit slashed, at severe hypoxia after the bigger dose of HC-030031. The TRPA1 function seemed specific for the hypoxic chemoreflex as neither the response to pure O2 nor hypercapnia was appreciably influenced by the TRPA1 antagonist.
Conclusions:
The study unravelled the role of TRPA1 in shaping the ventilatory response to low-intensity hypoxia, liable to be mediated by vagally innervated respiratory chemosensors of lower functional rank, but contradicted the TRPA1 being indispensable for the powerful carotid body chemoreflex in face of a severe hypoxic threat.
Insights
TRPA1 channel blockade dose-dependently reduced the hypoxic ventilatory response (HVR) in mice. This suggests TRPA1 channels are crucial for sensing mild hypoxia but not severe hypoxic threats.
Area of Science:
- Neuroscience
- Respiratory Physiology
Background:
- Transient Receptor Potential Ankyrin 1 (TRPA1) channels are implicated in sensing oxygen levels.
- TRPA1 channels are present in both peripheral and central nervous systems.
Purpose of the Study:
- To investigate the role of TRPA1 channels in the hypoxic ventilatory response (HVR).
- To test if TRPA1 channel blockade affects the HVR.
Main Methods:
- Conscious mice were administered a TRPA1 antagonist (HC-030031) at two doses.
- Ventilatory responses to mild (13% O2) and severe (7% O2) hypoxia, pure O2, and CO2 were measured using whole-body plethysmography.
Main Results:
- TRPA1 antagonism dose-dependently attenuated the HVR.
- Mild hypoxia response was nearly abolished, while severe hypoxia response was reduced but present.
- TRPA1 blockade did not significantly affect responses to pure O2 or hypercapnia.
Conclusions:
- TRPA1 channels play a role in the ventilatory response to low-intensity hypoxia.
- TRPA1 channels are not essential for the carotid body reflex during severe hypoxia.
