AUTHOR=Fukushi Isato , Takeda Kotaro , Pokorski Mieczyslaw , Kono Yosuke , Yoshizawa Masashi , Hasebe Yohei , Nakao Akito , Mori Yasuo , Onimaru Hiroshi , Okada Yasumasa 

TITLE=Activation of Astrocytes in the Persistence of Post-hypoxic Respiratory Augmentation

JOURNAL=Frontiers in Physiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.757731

DOI=10.3389/fphys.2021.757731

ISSN=1664-042X

ABSTRACT=<p>Acute hypoxia increases ventilation. After cessation of hypoxia loading, ventilation decreases but remains above the pre-exposure baseline level for a time. However, the mechanism of this post-hypoxic persistent respiratory augmentation (PHRA), which is a short-term potentiation of breathing, has not been elucidated. We aimed to test the hypothesis that astrocytes are involved in PHRA. To this end, we investigated hypoxic ventilatory responses by whole-body plethysmography in unanesthetized adult mice. The animals breathed room air, hypoxic gas mixture (7% O<sub>2</sub>, 93% N<sub>2</sub>) for 2min, and again room air for 10min before and after i.p. administration of low (100mg/kg) and high (300mg/kg) doses of arundic acid (AA), an astrocyte inhibitor. AA suppressed PHRA, with the high dose decreasing ventilation below the pre-hypoxic level. Further, we investigated the role of the astrocytic TRPA1 channel, a putative ventilatory hypoxia sensor, in PHRA using astrocyte-specific <italic>Trpa1</italic> knockout (as<italic>Trpa1</italic><sup>−/−</sup>) and floxed <italic>Trpa1</italic> (<italic>Trpa1</italic><sup>f/f</sup>) mice. In both <italic>Trpa1</italic><sup>f/f</sup> and as<italic>Trpa1</italic><sup>−/−</sup> mice, PHRA was noticeable, indicating that the astrocyte TRPA1 channel was not directly involved in PHRA. Taken together, these results indicate that astrocytes mediate the PHRA by mechanisms other than TRPA1 channels that are engaged in hypoxia sensing.</p>