The hypoxic ventilatory response and TRPA1 antagonism in conscious mice

M. Pokorski, K. Takeda, Y. Sato, Y. Okada

Research output: Contribution to journalArticle

19 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)928-938
Number of pages11
JournalActa Physiologica
Volume210
Issue number4
DOIs
Publication statusPublished - 01-01-2014
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology

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