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Astrocyte Kir4.1 Channels Contribute to Central Respiratory Drive
Author(s) -
Hawkins Virginia,
Mulkey Daniel
Publication year - 2015
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.29.1_supplement.860.12
Subject(s) - astrocyte , neuroscience , patch clamp , locus coeruleus , chemoreceptor , respiratory system , cerebellum , biology , electrophysiology , current clamp , control of respiration , chemistry , microbiology and biotechnology , central nervous system , anatomy , biochemistry , 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 express a H + ‐sensitive current mediated by a Kir4.1‐like conductance. The contribution of this pH sensitive current in RTN astrocytes to the central respiratory drive is as of yet unknown. Here we generate an inducible astrocyte specific Kir4.1 knockout (Kir4.1 cKO) by crossing GFAP‐CreERT2 and Kir4.1 floxed mouse lines. Immunohistochemical examination demonstrated recombination and reduction of Kir4.1 expression in GFAP positive cells in the hippocampus, cerebellum and RTN. Slice‐patch voltage clamp recordings of astrocytes from Kir4.1 cKO mice show the absence of a CO 2 /H + ‐sensitive current. Furthermore, plethysmography experiments show that Kir4.1 cKO animals breathe normally under control conditions in room air, but hypoventilate in 100% O 2 and exhibit a reduced tidal volume response to increased CO 2 compared to control mice. These results suggest that Kir4.1 channels in astrocytes contribute to the drive to breathe.