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Contribution of TRPA1 to arousal and respiratory activation to hypoxia


Kuroki, C.; Yonemitsu, T.; Kanmura, Y.; Kuwaki, T.

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European Journal of Anaesthesiology (EJA): June 2013 - Volume 30 - Issue - p 3-4
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Background and Goal of Study: TRPA1 (Transient receptor potential cation chanel, subfamilyA, member1), located in distal terminal of sensory neurons, is known to detect irritants and elicit airway defense response (pain, cough, respiratory arrest). In vagal nerve, TRPA1 detects 02 concentration and induces respiratory slowing. We hypothesized that TRPA1 also contributes to arousal from sleep and respiratory activation, as a defense response for hypoxia. To test our hypothesis, we measured arousal time and respiratory parameters around arousal response to hypoxia in mice indwelling EEG and EMG electrodes.

Materials and Methods: We used male TRPA1 knock out mice (TRPA1-KO) and wild-type mice (WT) (n=6, each). During natural sleeping, the continuous flushing air into the recording chamber was switched to hypoxic gas mixture (10% 02 balance with N2). 3minute of hypoxic challenge was repeated for 3times with an interval of at least 5min. The time to arousal was defined by change of EEG and EMG for over 5sec. Respiratory frequency and tidal volume was recorded using pneumotachograph, then minutes ventilation (MV) was calculated at every 5sec bins. Chamber 02 concentration was continuously monitored at the inlet of the chamber. The averaged data of 3 trials was considered as each mouse's data.

Results and Discussion: The time to arousal from natural sleep in response to hypoxia in TRPA1-KO was longerder than WT (114.2±20.1 vs. 30.0±10.1 sec). The increase of MV, just after arousal from sleep, was attenuated in TRPA1-KO than WT (0.38±0.18 vs. 1.2±0.35 ml/min/g).

Conclusion: TRPA1 contributes to arousal from natural sleep and respiratory activation for hypoxia. TRPA1 may, therefore, participate in pathophysiology of sleep apnea syndrome and sudden infant death syndrome since these syndromes are characterized as arousal deficient and breathing disorder around sleep.

© 2013 European Society of Anaesthesiology