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Acta Physiol (Oxf). 2014 Apr;210(4):928-38. doi: 10.1111/apha.12202. Epub 2013 Dec 12.

The hypoxic ventilatory response and TRPA1 antagonism in conscious mice.

Author information

1
Clinical Research Centre, National Hospital Organization Murayama Medical Center, Musashimurayama City, Japan; Medical Research Center, Polish Academy of Sciences, Warsaw, Poland.

Abstract

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.

KEYWORDS:

carotid chemoreceptors; chemosensing; hypercapnia; hyperventilation; hypoxia; oxygen sensor

PMID:
24245768
DOI:
10.1111/apha.12202
[Indexed for MEDLINE]

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