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Publication : Kir4.1 channels contribute to astrocyte CO(2)/H(+)-sensitivity and the drive to breathe.

First Author  Cleary CM Year  2024
Journal  Commun Biol Volume  7
Issue  1 Pages  373
PubMed ID  38548965 Mgi Jnum  J:349702
Mgi Id  MGI:7617415 Doi  10.1038/s42003-024-06065-0
Citation  Cleary CM, et al. (2024) Kir4.1 channels contribute to astrocyte CO(2)/H(+)-sensitivity and the drive to breathe. Commun Biol 7(1):373
abstractText  Astrocytes in the retrotrapezoid nucleus (RTN) stimulate breathing in response to CO(2)/H(+), however, it is not clear how these cells detect changes in CO(2)/H(+). Considering Kir4.1/5.1 channels are CO(2)/H(+)-sensitive and important for several astrocyte-dependent processes, we consider Kir4.1/5.1 a leading candidate CO(2)/H(+) sensor in RTN astrocytes. To address this, we show that RTN astrocytes express Kir4.1 and Kir5.1 transcripts. We also characterized respiratory function in astrocyte-specific inducible Kir4.1 knockout mice (Kir4.1 cKO); these mice breathe normally under room air conditions but show a blunted ventilatory response to high levels of CO(2), which could be partly rescued by viral mediated re-expression of Kir4.1 in RTN astrocytes. At the cellular level, astrocytes in slices from astrocyte-specific inducible Kir4.1 knockout mice are less responsive to CO(2)/H(+) and show a diminished capacity for paracrine modulation of respiratory neurons. These results suggest Kir4.1/5.1 channels in RTN astrocytes contribute to respiratory behavior.
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