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Conditional knockdown of Kir4.1 in astrocytes blunts the hypercapnic respiratory response in awake mice (872.7)
Author(s) -
Hawkins Virginia,
Kuo Fushan,
Bellemare Laura,
Perez Diana,
Dubreuil Todd,
Mulkey Daniel
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.872.7
Subject(s) - astrocyte , chemoreceptor , control of respiration , carotid body , respiratory system , depolarization , gene knockdown , neuroscience , chemistry , tidal volume , hypoxic ventilatory response , biology , medicine , endocrinology , anatomy , electrophysiology , central nervous system , biochemistry , apoptosis , receptor
Central chemoreception is the mechanisms by which the brain regulates breathing in response to changes in tissue CO 2 /H + . The retrotrapezoid nucleus (RTN) has been identified as a key locus for central respiratory control. Neurons in this region sense CO 2 /H + in part by inhibition of TASK‐2 channels. RTN astrocytes are also chemosensitive and CO 2 ‐ evoked release of the gliotransmitter ATP most likely occurs via hemichannels. However, RTN astrocytes also respond to bath acidification with ~8 mV depolarization, which is mediated by inhibition of a Kir4.1‐like conductance. The contribution of this pH sensitive current in RTN astrocytes to central respiratory drive is yet to be determined. Here we generate a tamoxifen inducible, astrocyte specific Kir4.1 knockout (ciKir4.1KO) by crossing GFAP‐CreERT2 and a Kir4.1 floxed mouse lines. Whole‐body plethysmography experiments performed on 6 week old mice show that ciKir4.1KO animals breathe normally control conditions but exhibit a reduced tidal volume response to CO 2 compared to tamoxifen treated GFAP‐CreERT2 Kir4.1 wild type (i.e., control) mice. These results suggest that Kir4.1 channels in astrocytes contribute to the CO 2 ventilatory response in awake mice. Grant Funding Source : NIH HL104101 (DKM)