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K ir 5. 1‐dependent CO 2 /H + ‐sensitive currents contribute to astrocyte heterogeneity across brain regions
Author(s) -
Patterson Kelsey C.,
Kahanovitch Uri,
Gonçalves Christopher M.,
Hablitz John J.,
Staruschenko Alexander,
Mulkey Daniel K.,
Olsen Michelle L.
Publication year - 2021
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.23898
Subject(s) - astrocyte , depolarization , biology , neuroscience , electrophysiology , biophysics , brainstem , potassium channel , membrane potential , microbiology and biotechnology , central nervous system
Astrocyte heterogeneity is an emerging concept in which astrocytes within or between brain regions show variable morphological and/or gene expression profiles that presumably reflect different functional roles. Recent evidence indicates that retrotrapezoid nucleus (RTN) astrocytes sense changes in tissue CO 2/ H + to regulate respiratory activity; however, mechanism(s) by which they do so remain unclear. Alterations in inward K + currents represent a potential mechanism by which CO 2 /H + signals may be conveyed to neurons. Here, we use slice electrophysiology in rats of either sex to show that RTN astrocytes intrinsically respond to CO 2 /H + by inhibition of an inward rectifying potassium (K ir ) conductance and depolarization of the membrane, while cortical astrocytes do not exhibit such CO 2 /H + ‐sensitive properties. Application of Ba 2+ mimics the effect of CO 2 /H + on RTN astrocytes as measured by reductions in astrocyte K ir ‐like currents and increased RTN neuronal firing. These CO 2 /H + ‐sensitive currents increase developmentally, in parallel to an increased expression in K ir 4.1 and K ir 5.1 in the brainstem. Finally, the involvement of K ir 5.1 in the CO 2 /H + ‐sensitive current was verified using a Kir5.1 KO rat. These data suggest that K ir inhibition by CO 2 /H + may govern the degree to which astrocytes mediate downstream chemoreceptive signaling events through cell‐autonomous mechanisms. These results identify K ir channels as potentially important regional CO 2 /H + sensors early in development, thus expanding our understanding of how astrocyte heterogeneity may uniquely support specific neural circuits and behaviors.